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Markers to measure immunomodulation in human nutrition intervention studies

Published online by Cambridge University Press:  08 March 2007

Ruud Albers ,
Jean-Michel Antoine ,
Raphaëlle Bourdet-Sicard ,
Philip C. Calder ,
Michael Gleeson ,
Bruno Lesourd ,
Sonia Samartín ,
Ian R. Sanderson ,
Jan Van Loo  and
F. Willem Vas Dias
...Show all authors
Ruud Albers
Affiliation:
Unilever Health Institute, PO Box 114, NL 3130 AC, Vlaardingen, The Netherlands
Jean-Michel Antoine
Affiliation:
Danone Vitapole – Nutrivaleur, Route Départementale 128, F-91767, Palaiseau, cedex, France
Raphaëlle Bourdet-Sicard
Affiliation:
Danone Vitapole – Nutrivaleur, Route Départementale 128, F-91767, Palaiseau, cedex, France
Philip C. Calder
Affiliation:
University of Southampton, Institute of Human Nutrition, Faculty of Medicine, Bassett Crescent East, Southampton, SO16 7PX, UK
Michael Gleeson
Affiliation:
Loughborough University, School of Sport & Exercise Sciences, Loughborough, LE11 3TU, UK
Bruno Lesourd
Affiliation:
Hôpital Universitaire de Clermont-Ferrand, Service Soins de Suite, Route de Châteaugay BP 56, F-63118, Cebazat, France
Sonia Samartín*
Affiliation:
ILSI Europe, 83 Av. E. Mounier Box 6, B-1200, Brussels, Belgium
Ian R. Sanderson
Affiliation:
Research Centre in Gastroenterology, Institute of Cell and Molecular Science, Barts and the London, Queen Mary School of Medicine and Dentistry, Turner Street, London, E1 2AD, UK
Jan Van Loo
Affiliation:
Raffinerie Tirlemontoise, Orafti, Aandorenstraat 1, B-3300, Tienen, Belgium
F. Willem Vas Dias
Affiliation:
Seven Seas Ltd, Hedon Road, Marfleet, Hull, HU9 5NJ, UK
Bernhard Watzl
Affiliation:
Federal Research Centre for Nutrition and Food, Institute of Nutritional Physiology, Haid-und-Neu-Strasse, D-76131, Karlsruhe, Germany
*
*Corresponding author: Dr S. Samartin, fax +32 2 762 00 44, email publications@ilsieurope.be
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Abstract

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Normal functioning of the immune system is crucial to the health of man, and diet is one of the major exogenous factors modulating individual immunocompetence. Recently, nutrition research has focused on the role of foods or specific food components in enhancing immune system responsiveness to challenges and thereby improving health and reducing disease risks. Assessing diet-induced changes of immune function, however, requires a thorough methodological approach targeting a large spectrum of immune system parameters. Currently, no single marker is available to predict the outcome of a dietary intervention on the resistance to infection or to other immune system-related diseases. The present review summarises the immune function assays commonly used as markers in human intervention studies and evaluates their biological relevance (e.g. known correlation with clinically relevant endpoints), sensitivity (e.g. within- and between-subject variation), and practical feasibility. Based on these criteria markers were classified into three categories with high, medium or low suitability. Vaccine-specific serum antibody production, delayed-type hypersensitivity response, vaccine-specific or total secretory IgA in saliva and the response to attenuated pathogens, were classified as markers with high suitability. Markers with medium suitability include natural killer cell cytotoxicity, oxidative burst of phagocytes, lymphocyte proliferation and the cytokine pattern produced by activated immune cells. Since no single marker allows conclusions to be drawn about the modulation of the whole immune system, except for the clinical outcome of infection itself, combining markers with high and medium suitability is currently the best approach to measure immunomodulation in human nutrition intervention studies. It would be valuable to include several immune markers in addition to clinical outcome in future clinical trials in this area, as there is too little evidence that correlates markers with global health improvement.

Keywords

Immune functionMarkerDietHuman studiesInfections

Information

Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 3 , September 2005 , pp. 452 - 481
Copyright
Copyright © The Nutrition Society 2005

References

Albert, MA & Ridker, PM (1999) The role of C-reactive protein in cardiovascular disease risk. Curr Cardiol Rep 1, 99–104.CrossRefGoogle ScholarPubMed
Allsopp, CEM, Nicholls, SJ & Langhorne, J (1998) A flow cytometric method to assess antigen-specific proliferative responses of different subpopulations of fresh and cryopreserved human peripheral blood mononuclear cells. J Immunol Methods 214, 175–186.CrossRefGoogle ScholarPubMed
Ananworanich, J & Shearer, WT (2002) Delayed-type hypersensitivity skin testing.In Manual of Clinical Laboratory Immunology 6th ed. 212–219Rose, NR, Hamilton, B, Detrick, B, editors]. Washington, DC ASM PressGoogle Scholar
Arreaza, EE, Gibbons, JJ, Sisking, GW & Weksler, ME (1993) Lower antibody response to tetanus toxoid associated with higher auto-anti-idiotype antibody in old compared to young humans. Clin Exp Immunol 92, 169–176.CrossRefGoogle Scholar
Azim, T, Islam, LN, Sarker, MS, Ahmad, SM, Hamadani, JD, Faruque, SM & Salam, MA (2000) Immune response of Bangladeshi children with acute diarrhea who subsequently have persistent diarrhea. J Pediatr Gastroenterol Nutr 31, 528–535.Google ScholarPubMed
Aziz, M, Akhtar, S & Malik, A (1998) Evaluation of cell-mediated immunity and circulating immune complexes as prognostic indicators in cancer patients. Cancer Detect Prev 22, 87–99.CrossRefGoogle ScholarPubMed
Beery, TA (2003) Sex differences in infection and sepsis. Crit Care Nurs Clin North Am 15, 55–62.CrossRefGoogle Scholar
Berk, LS, Ton, SA, Nieman, DC & Eby, EC (1986) The suppressive effect of stress from acute exhaustive exercise on T-lymphocyte helper/suppressor ratio in athletes and non-athletes. Med Sci Sports Exerc 18, 706–710.CrossRefGoogle Scholar
Beutler, B (2004) Innate immunity: an overview. Mol Immunol 40, 845–859.CrossRefGoogle ScholarPubMed
Bienvenu, J, Monneret, G, Fabien, N & Revillard, JP (2000) The clinical usefulness of the measurement of cytokines. Clin Chem Lab Med 38, 267–285.CrossRefGoogle ScholarPubMed
Blannin, AK, Chatwin, LJ, Cave, R & Gleeson, M (1996) Effects of submaximal cycling and long-term endurance training on neutrophil phagocytic activity in middle-aged men. Br J, SportsM, ed 30, 125–129.CrossRefGoogle ScholarPubMed
Blatt, SP, Hendrix, CW, Butzin, CA, Freeman, TM, Ward, WW, Hensley, RE, Melcher, GP, Donovan, DJ & Boswell, RN (1993) Delayed-type hypersensitivity skin testing predicts progression to AIDS in HIV-infected patients. Ann Intern Med 119, 177–184.CrossRefGoogle ScholarPubMed
Bloemena, E, Roos, MT, Van Heijst, JL, Vossen, JM & Schellekens, PT (1989) Whole-blood lymphocyte cultures. J Immunol Methods 122, 161–167.CrossRefGoogle ScholarPubMed
Bogden, JD, Oleske, JM, Lavenhar, MA, Munves, EM, Kemp, FW, Bruening, KS, Holding, KJ, Denny, TN, Guarino, MA & Holland, BK (1990) Effects of one year supplementation with zinc and other micronutrients on cellular immunity in the elderly. J Am Coll Nutr 9, 214–225.CrossRefGoogle ScholarPubMed
Bogden, JD, Bendich, A, Kemp, FW, Bruening, KS, Skurnick, JH, Denny, T, Baker, H & Louria, DB (1994) Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people. Am J, Clin Nutr 60, 437–447.CrossRefGoogle ScholarPubMed
Bouman, A, Schipper, M, Heineman, MJ & Faas, MM (2004) Gender difference in the non-specific and specific immune response in humans. Am J, Reprod Immunol 52, 19–26.CrossRefGoogle ScholarPubMed
Bovee-Oudenhoven, IM, Lettink-Wissink, ML, Van Doesburg, W, Witteman, BJ, Van, DMeer, R (2003) Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium. Gastroenterology 125, 469–476.CrossRefGoogle ScholarPubMed
Brabin, L (2002) Interactions of the female hormone environment, susceptibility to viral infections, and disease progression. AIDS Patient Care STDS 16, 211–221.CrossRefGoogle ScholarPubMed
Bradley, JA, Ledingham, IM & Hamilton, DN (1981) Assessment of host resistance in critically ill surgical patients by the response to recall skin antigens. Intensive Care Med 7, 105–108.CrossRefGoogle ScholarPubMed
Broadbent, DE, Broadbent, MH, Phillpotts, RJ & Wallace, J (1984) Some further studies on the prediction of experimental colds in volunteers by psychological factors. J Psychosom Res 28, 511–523.CrossRefGoogle ScholarPubMed
Bruunsgaard, H, Hartkopp, A, Mohr, T, Konradsen, H, Heron, I, Mordhorst, CH & Pedersen, BK (1997) In vivo cell-mediated immunity and vaccination response following prolonged, intense exercise. Med Sci Sports Exerc 29, 1176–1181.CrossRefGoogle ScholarPubMed
Burdge, GC & Calder, PC (2005) Plasma cytokine response during the postprandial period: a potential causal process in vascular disease?. Br J Nutr 93, 3–9.CrossRefGoogle ScholarPubMed
Cakman, I, Rohwer, J, Schutz, RM, Kirchner, H & Rink, L (1996) Dysregulation between TH1 and TH2 cell sub-populations in the elderly. Mech Ageing Dev 87, 197–209.CrossRefGoogle Scholar
Calder, PC & Field, CJ (2002) Fatty acids, inflammation and immunity.In Nutrition and Immune Function pp.57 –92 [Calder, PC, Field, CJ, Gill, HS, editors]. OxfordCABI Publishing.CrossRefGoogle Scholar
Calder, PC & Kew, S (2002) The immune system: a target for functional foods?. Br J Nutr 88 Suppl. 2 S165–S177CrossRefGoogle ScholarPubMed
Ceddia, MA & Woods, J (1999) Exercise suppresses macrophage antigen presentation. J Appl Physiol 87, 2253–2258.CrossRefGoogle ScholarPubMed
Chandra, RK (1984) Excessive intake of zinc impairs immune responses. JAMA 52, 1443–1446.CrossRefGoogle Scholar
Chandra, RK (1991) 1990 McCollum Award Lecture: Nutrition and immunity: lessons from the past and new insights into the future. Am J, Clin Nutr 53, 1087–1101.CrossRefGoogle ScholarPubMed
Chandra, RK (1992) Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 340, 1124–1127.CrossRefGoogle ScholarPubMed
Chang, L, Gusewitch, GA, Chritton, DB, Folz, JC, Lebeck, LK, Nehlsen-Cannarella, SL (1993) Rapid flow cytometric assay for the assessment of natural killer cell activity. J Immunol Methods 166, 45–54.CrossRefGoogle ScholarPubMed
Christou, NV, Meakins, JL, Gordon, J, Yee, J, Hassan-Zahraee, M, Nohr, CW, Shizgal, HM, MacLean, LD (1995) The delayed hypersensitivity response and host resistance in surgical patients: 20 years later. Ann Surg 222, 534–546.CrossRefGoogle ScholarPubMed
Cohen, S, Tyrrell, DA & Smith, AP (1991) Psychological stress and susceptibility to the common cold. N Eng J Med 325, 606–612.CrossRefGoogle ScholarPubMed
Cossarizza, A, Ortolani, C & Paganelli, R (1992) Age-related imbalance of virgin (CD45RA + ) and memory (CD45RO + ) cells between CD4 + and CD8 + T lymphocytes in humans: study from newborns to centenarians. J Immunol Res 4, 117–126.Google Scholar
Cross, NA, Shetty, G, Nordstrom, JW, Davis, CA & Kramer, TR (1998) Effects of mixed-carotenoid supplementation on plasma carotene concentrations and T lymphocyte immunocompetence in elderly black women. FASEB J 12 A857 AbstrGoogle Scholar
Cummings, JH, Antoine, J-M & Aspiroz, F (2004) PASSCLAIM – Gut health and immunity. Eur J Nutr 43 Suppl. 2 118–173CrossRefGoogle ScholarPubMed
Curotto de Lafaille, MA & Lafaille, JJ (2002) CD4 (+) regulatory T cells in autoimmunity and allergy. Curr Opin Immunol 14, 771–778.CrossRefGoogle ScholarPubMed
Dandona, P, Aljada, A & Bandyopadhyay, A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25, 4–7.CrossRefGoogle ScholarPubMed
Decker, T, Lohmann-Matthes, ML (1988) A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 115, 61–69.CrossRefGoogle ScholarPubMed
Dean, PA & Elson, CD (1997) Immunology.In Surgery of the Colon and Rectum.pp. 57 [Nicholls, RJ, Dozois, RR, editors]. New York: Churchill Livingstone.Google Scholar
Delacroix, DL, Dive, C, Rambaud, JC & Vaerman, JP (1982) IgA subclasses in various secretions and in serum. Immunology 47, 383–385.Google ScholarPubMed
Elsasser-Beile, Uvon Kleist, S & Gallati, H (1991) Evaluation of a test system for measuring cytokine production in human whole blood cell cultures. J Immunol Methods 139, 191–195.CrossRefGoogle ScholarPubMed
Faas, M, Bouman, A, Moesa, H, Heineman, MJ, de Leij, L (2000) Schuiling G The immune response during the luteal phase of the ovarian cycle: a TH2-type response. Fertil Steril 74, 1008–1013.CrossRefGoogle ScholarPubMed
Fidel, PL Jr (2002) Immunity to Candida. Oral Dis 8 Suppl. 2 69–75.CrossRefGoogle ScholarPubMed
Fietta, A, Merlini, C, Dos, SC, Rovida, S & Grassi, C (1994) Influence of aging on some specific and nonspecific mechanisms of the host defense system in 146 healthy subjects. Gerontology 40, 237–245.CrossRefGoogle ScholarPubMed
Fletcher, MA & Saliou, P (2000) Vaccines and infectious disease. EXS 89, 69–88.Google ScholarPubMed
Fritscher-Ravens, A & Swain, CP (2002) The wireless capsule: new light in the darkness. Dig Dis 20 Suppl. 2 127–133.CrossRefGoogle ScholarPubMed
Fujiwara, S, Akiyama, M, Yamakido, M, Seyama, T, Kobuke, K, Hakoda, M, Kyoizumi, S & Jones, SL (1986) Cryopreservation of human lymphocytes for assessment of lymphocyte subsets and natural killer cytotoxicity. J Immunol Methods 90, 265–273.Google ScholarPubMed
Fuller, CJ, Faulkner, H, Bendich, A, Parker, RS & Roe, DA (1992) Effect of β-carotene supplementation on photosuppression of delayed-type hypersensitivity in normal young men. Am J Clin Nutr 56, 684–690.CrossRefGoogle ScholarPubMed
Gaines, H, Andersson, L & Biberfeld, G (1996) A new method for measuring lymphoproliferation at the single-cell level in whole blood cultures by flow cytometry. J Immunol Methods 195, 63–72.CrossRefGoogle ScholarPubMed
Gannon, GA, Rhind, S, Shek, PN & Shephard, RJ (2002) Naïve and memory T cell subsets are differentially mobilized during physical stress. Int J Sports Med 23, 223–229.CrossRefGoogle ScholarPubMed
Gardner, EM & Murasko, DM (2002) Age-related changes in type 1 and type 2 cytokine production in humans. Biogerontology 3, 271–290.CrossRefGoogle ScholarPubMed
Gill, HS & Cross, ML (2002) Probiotics and immune function. In Nutrition and Immune Function, pp. 251–272 [Calder, PC, Fields, CJ and Gill, HS, editors]. Oxford: CABI Publishing.CrossRefGoogle Scholar
Girardin, SE & Philpott, DJ (2004) Mini-review: the role of peptidoglycan recognition in innate immunity. Eur J Immmunol 34, 1777–1782.CrossRefGoogle ScholarPubMed
Gleeson, M (2000) Mucosal immune responses and risk of respiratory illness in elite athletes. Exerc Immunol Rev 6, 5–42.Google ScholarPubMed
Gleeson, M (2004) Immune function and exercise. Eur J Sport Sci 4, 52–61.CrossRefGoogle Scholar
Gleeson, M & Bishop, NC (1999) Immunology. In Basic and Applied Sciences for Sports Medicine, pp. 199–236 [Maughan, RJ, editor]. Oxford: Butterworth Heinemann.Google Scholar
Gordin, FM, Hartigan, PM, Klimas, NG, Zolla-Pazner, SB, Simberkoff, MS & Hamilton, JD (1994) Delayed-type hypersensitivity skin tests are an independent predictor of human immunodeficiency virus disease progression. Department of Veterans Affairs Cooperative Study Group. J Infect Dis 169, 893–897.CrossRefGoogle ScholarPubMed
Graat, JM, Schouten, EG & Kok, FJ (2002) Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized control trial. JAMA 288, 715–721.CrossRefGoogle Scholar
Hamrick, N, Cohen, S & Rodriguez, MS (2002) Being popular can be healthy or unhealthy: stress, social network diversity, and incidence of upper respiratory tract infection. Health Psychol 21, 294–298.CrossRefGoogle ScholarPubMed
Haus, E & Smolensky, MH (1999) Biologic rhythms in the immune system. Chronobiol Int 16, 581–622.CrossRefGoogle ScholarPubMed
Hayek, GM, Mura, C, Wu, D, Beharka, AA, Han, SN, Paulson, E, Hwang, D & Meydani, SN (1997) Enhanced expression of inducible cyclooxygenase with age in murine macrophages. J Immunol 159, 1445–1451.CrossRefGoogle ScholarPubMed
Heath, GW, Ford, ES, Craven, TE, Macera, CA, Jackson, KL & Pate, RR (1991) Exercise and the incidence of upper respiratory tract infections. Med Sci Sports Exerc 23, 152–157.CrossRefGoogle ScholarPubMed
Herraiz, LA, Hsieh, WC, Parker, RS, Swanson, JE, Bendich, A & Roe, DA (1998) Effect of UV exposure and β-carotene supplementation on delayed-type hypersensitivity response in healthy older men. J Am Coll Nutr 17, 617–624.CrossRefGoogle ScholarPubMed
Hofmann, B, Bygbjerg, I, Dickmeiss, E, Faber, V, Frederiksen, B, Gaub, J, Gerstoft, J, Jakobsen, BK, Jakobsen, KD & Lindhardt, BO (1989) Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging. Scand J Infect Dis 21, 633–643.CrossRefGoogle ScholarPubMed
Hutchinson, P, Divola, LA & Holdsworth, SR (1999) Mitogen-induced T-cell CD69 expression is a less sensitive measure of T-cell function than [3H]-thymidine uptake. Cytometry 38, 244–249.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
Imai, K, Matsuyama, S, Miyake, S, Suga, K & Nakachi, K (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356, 1795–1799.CrossRefGoogle ScholarPubMed
Isaacs, D, Webster, ADB & Valman, HB (1984) Immunoglobulin levels and function in preschool children with recurrent respiratory infections. Clin Exp Immunol 58, 335–340.Google ScholarPubMed
Janeway, CA, Travers, P, Walport, M & Shlomchik, M (2005) Immunobiology, 6th ed. London: Garland Publishing.Google Scholar
Jemmott, JB, Borysenko, JZ, Borysenko, M, McClelland, DC, Chapman, R, Meyer, D & Benson, H (1983) Academic stress, power motivation, and decrease in secretion rate of salivary secretory immunoglobulin A. Lancet 1, 1400–1402.CrossRefGoogle ScholarPubMed
Jewett, MA, Gupta, S, Hansen, JA, Cunningham-Rundles, S, Siegal, FP, Good, RA & Dupont, B (1976) The use of cryopreserved lymphocytes for longitudinal studies of immune function and enumeration of subpopulations. Clin Exp Immunol 25, 449–454.Google ScholarPubMed
Keil, D, Luebke, RW & Pruett, SB (2001) Quantifying the relationship between multiple immunological parameters and host resistance: probing the limits of reductionism. J Immunol 167, 4543–4552.CrossRefGoogle ScholarPubMed
Komatsu, M, Kobayashi, D, Saito, K, Furuya, D, Yagihashi, A, Araake, H, Tsuji, N, Sakamaki, S, Niitsu, Y & Watanabe, N (2001) Tumor necrosis factor-a in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR. Clin Chem 47, 1297–1301.CrossRefGoogle Scholar
Konjevic, G, Jurisic, V & Spuzic, I (1997) Corrections to the original lactate dehydrogenase (LDH) release assay for the evaluation of NK cell cytotoxicity. J Immunol Methods 200, 199–201.CrossRefGoogle Scholar
Kramer, TR & Burri, BJ (1997) Modulated mitogenic proliferative responsiveness of lymphocytes in whole-blood cultures after a low-carotene diet and mixed-carotenoid supplementation in women. Am J Clin Nutr 65, 871–875.CrossRefGoogle ScholarPubMed
Kruse, N & Rieckmann, P (2002) Molecular analysis of cytokines and cytokine receptors. In Manual of Clinical Laboratory Immunology, 6th ed. 347–356 [Rose, NR, Hamilton, B and Detrick, B, editors]. Washington, DC: ASM Press.Google Scholar
Kuritzkes, DR (2000) Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: the role of granulocyte colony-stimulating factor. Clin Infect Dis 30, 256–260.CrossRefGoogle ScholarPubMed
Lancaster, GL, Halson, SL, Khan, Q, Drysdale, P, Jeukendrup, AE, Drayson, MT & Gleeson, M (2003 a) Effect of acute exhaustive exercise and a 6-day period of intensified training on immune function in cyclists. J Physiol 548, O96.Google Scholar
Lancaster, GL, Halson, SL, Khan, Q, Drysdale, P, Jeukendrup, AE, Drayson, MT & Gleeson, M (2003 b) Effect of exhaustive exercise and intensified training on human T-lymphocyte CD45RO expression. J Physiol 548, O97.Google Scholar
Lancaster, GL, Khan, Q, Drysdale, P, Jeukendrup, AE, Drayson, MT & Gleeson, M (2003 c) The effect of exercise on the expression and function of human monocyte toll-like receptors. J Physiol 555, C112.Google Scholar
Lehmann, AK, Sornes, S & Halstensen, A (2000) Phagocytosis: measurement by flow cytometry. J Immunol Methods 243, 229–242.CrossRefGoogle ScholarPubMed
Leroux-Roels, G, Van Hecke, E, Michielsen, W, Voet, P, Hauser, P & Petre, J (1994) Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines. Vaccine 12, 812–818.CrossRefGoogle ScholarPubMed
Lesourd, B (1999) Immune responses during diseases and recovery in the elderly. Proc Nutr Soc 58, 1–14.CrossRefGoogle ScholarPubMed
Lesourd, B (2000) Undernutrition: a factor of accelerated ageing in healthy and diseased aged persons. In Handbook of Nutrition in the Aged Persons, pp. 145–158 [Watson, RR, editor]. New York: CRC Press.CrossRefGoogle Scholar
Lesourd, BM, Wang, A & Moulias, R (1985) Serial delayed cutaneous hypersensitivity skin testing with multiple recall antigens in healthy volunteers: booster effect study. Ann Allergy 55, 729–735.Google ScholarPubMed
Lesourd, BM, Mazari, L & Ferry, M (1998) The role of nutrition in immunity in the aged. Nutr Rev 56, S113–S125.CrossRefGoogle ScholarPubMed
Lesourd, B, Raynaud-Simon, A & Mazari, L (2002) Nutrition and ageing of the immune system. In Nutrition and Immune Function, pp. 357–374 [Calder, PC, Field, CJ and Gill, HS, editors]. Oxford: CABI Publishing.CrossRefGoogle Scholar
Levy, SM, Herberman, RB, Lee, J, Whiteside, T, Beadle, M, Heiden, L & Simons, A (1991) Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Nat Immun Cell Growth Regul 10, 289–307.Google ScholarPubMed
Liebmann, PM, Reibnegger, G, Lehofer, M, Moser, M, Purstner, P, Mangge, H & Schauenstein, K (1998) Circadian rhythm of the soluble p75 tumor necrosis factor (sTNF-R75) receptor in humans – a possible explanation for the circadian kinetics of TNF-α effects. Int Immunol 10, 1393–1396.CrossRefGoogle Scholar
Liew, FY (2002) T(H)1 and T(H)2 cells: a historical perspective. Nature Rev Immunol 2, 55–60.CrossRefGoogle Scholar
Ligthart, GJ, Corberand, JX, Fournier, C, Galanaud, P, Hijmans, W, Kennes, B, Muller-Hermelink, HK & Steinmann, GG (1984) Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 28, 47–55.CrossRefGoogle ScholarPubMed
Lord, JM, Butcher, S, Killampali, V, Lascelles, D & Salmon, M (2001) Neutrophil ageing and immunesenescence. Mech Ageing Dev 122, 1521–1535.CrossRefGoogle ScholarPubMed
Lyons, AB (2000) Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J Immunol Methods 243, 147–154.CrossRefGoogle ScholarPubMed
Mackinnon, LT (1999) Advances in Exercise and Immunology Champaign, IL Human KineticsGoogle Scholar
MacLean, LD (1988) Delayed type hypersensitivity testing in surgical patients Surg Gynecol Obstet 166, 285–293.Google ScholarPubMed
MacLennan, ICM & Drayson, MT (1999) Normal lymphocytes and non-neoplastic lymphocyte disorders. In Postgraduate Haematology 4th ed. 296 – 298 [Hoffbrand, AV, Lewis, SM, Tuddenham, EGDOxford: Butterworth Heinemann.Google Scholar
Maloy, KJ & Powrie, F (2001) Regulatory T cells in the control of immune pathology. Nat Immunol 2,, 816–822.CrossRefGoogle ScholarPubMed
Maloy, KJ, Salaun, L, Cahill, R, Dougan, G, Saunders, NJ & Powrie, F (2003) CD4 + CD25 + T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 197, 111–119.CrossRefGoogle ScholarPubMed
Mann, DR, Akinbami, MA, Gould, KG & Ansari, AA (2000) Seasonal variation in cytokine expression and cell-mediated immunity in male rhesus monkeys. Cell Immunol 200, 105–115.CrossRefGoogle ScholarPubMed
Marrie, TJ, Johnson, S & Durant, H (1988) Cell-mediated immunity of healthy adult Nova Scotians in various age groups compared with nursing home and hospitalized senior citizens. J Allergy Clin Immunol 81, 836–843.CrossRefGoogle ScholarPubMed
Martinon, F, Rabian, C, Loiseau, P, Ternynck, TAvrameas, S & Colombani, J (1987) In vitro proliferation of human lymphocytes measured by an enzyme immunoassay using an anti-5-bromo-2-deoxyuridine monoclonal antibody. J Clin Lab Immunol 23, 153–159.Google ScholarPubMed
Matthews, CE, Ockene, IS, Freedson, PS, Rosal, MC, Merriam, PA & Hebert, JR (2002) Moderate to vigorous physical activity and the risk of upper-respiratory tract infection. Med Sci Sports Exerc 34, 1242–1248.CrossRefGoogle ScholarPubMed
Mazari, L & Lesourd, B (1998) Nutritional influence on immune response in healthy aged persons. Mech Ageing Dev 100, 17–32.Google Scholar
Messele, T, Roos, MT, Hamann, D, Koot, M, Fontanet, AL, Miedema, F, Schellekens, PT & Rinke de Wit, TF (2000) Nonradioactive techniques for measurement of in vitro T-cell proliferation: alternatives to the [3 H]thymidine incorporation assay. Clin Diagn Lab Immunol 7, 687–692.CrossRefGoogle Scholar
Meyaard, L, Kuiper, H, Otto, SA, Wolthers, KC, Van Lier, RA & Miedema, F (1995) Evidence for intact costimulation via CD28 and CD27 molecules in hyporesponsive T cells from human immunodeficiency virus-infected individuals. Eur J Immunol 25, 232–237.CrossRefGoogle ScholarPubMed
Meydani, SN, Barklund, MP, Liu, S, Meydani, M, Miller, RA, Cannon, JG, Morrow, FD, Rocklin, R & Blumberg, JB (1990) Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J, Clin Nutr 52, 557–563.CrossRefGoogle ScholarPubMed
Meydani, SN, Meydani, M, Blumberg, JB, Lekal, S, Siber, G, Loszewski, R, Thompson, C, Pedrosa, C, Diamond, RD & Stollar, BD (1997) Vitamin E supplementation and in vivo immune responses in healthy elderly individuals. JAMA 277, 1380–1386.CrossRefGoogle Scholar
Moynihan, JA, Callahan, TA, Kelley, SP & Campbell, LM (1998) Adrenal hormone modulation of type 1 and type 2 cytokine production by spleen cells: dexamethasone and dehydroepiandrosterone suppress interleukin-2, interleukin-4, and interferon-gamma production in vitro. Cell Immunol 184, 58–64.CrossRefGoogle ScholarPubMed
Murasko, DM, Weiner, P & Kaye, D, (1987) Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol 70, 440–448.Google ScholarPubMed
Mylonaki, M, Fritscher-Ravens, A & Swain, P, (2003) Wireless capsule endoscopy: a comparison with push enteroscopy in patiens with gastroscopy and colonoscopy negative gastrointestinal bleeding. Gut 52, 1122–1126.CrossRefGoogle Scholar
Myrianthefs, P, Karatzas, S, Venetsanou, K, Grouzi, E, Evagelopoulou, P, Boutzouka, E, Fildissis, G, Splilotopoulou, I & Baltopoulos, G (2003) Seasonal variation in whole blood cytokine production after LPS stimulation in normal individuals. Cytokine 24, 286–292.CrossRefGoogle ScholarPubMed
Nagao, F, Yabe, T, Xu, M, Yokoyama, K, Saito, K & Okumura, K (1996) Application of non-radioactive europium (Eu 3+ ) release assay to a measurement of human natural killer activity of healthy and patient populations. Immunol Invest 25, 507–518.CrossRefGoogle Scholar
Nelson, RJ (2004) Seasonal immune function and sickness responses. Trends Immunol 25, 187–192.CrossRefGoogle ScholarPubMed
Nelson, RJ & Demas, GE (1996) Seasonal changes in immune function. Q Rev Biol 71, 511–548.CrossRefGoogle ScholarPubMed
Nieman, DC (1994) Exercise, infection and immunity. Int J, Sports M ed 15, S131–S141.CrossRefGoogle ScholarPubMed
Nieman, DC, Johansen, LM, Lee, JW & Arabatzis, K (1990) Infectious episodes in runners before and after the Los Angeles Marathon. J Sports Med Phys Fitness 30, 316–328.Google ScholarPubMed
Niess, AM, Dickhuth, H-H, Northoff, H & Fehrenbach, E (1999) Free radicals and oxidative stress in exercise – immunological aspects. Exerc Immunol Rev 5, 22–56.Google ScholarPubMed
Nisbet-Brown, ER, Lee, JW, Cheung, RK & Gelfand, EW (1987) Antigen-specific and -nonspecific mitogenic signals in the activation of human T cell clones. J Immunol 138, 3713–3719.CrossRefGoogle ScholarPubMed
Northoff, H, Berg, A & Weinstock, C (1998) Similarities and differences of the immune response to exercise and trauma: the IFN-γ concept. Can J Physiol Pharmacol 76, 497–504.CrossRefGoogle ScholarPubMed
O'Gorman, MRG (2002) Evaluation of phagocytic cell function. In Manual of Clinical Laboratory Immunology, 6th ed., pp. 265–273 [Rose, NR, Hamilton, B and Detrick, B, editors]. Washington, DC: ASM Press.Google Scholar
Ogata, K, An, E, Shioi, Y, Nakamura, K, Luo, S, Yokose, N, Minami, S & Dan, K (2001) Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol 124, 392–397.CrossRefGoogle ScholarPubMed
Ouellette, AJ & Bevins, CL (2000) Development of innate immunity in the small intestine. In Development of the Gastrointestinal Tract, pp. 147–164 [Sanderson, IR and Walker, WA, editors]. Hamilton, BC: Decker.Google Scholar
Paavonen, T (1994) Hormonal regulation of immune responses. Ann Med 26, 255–258.CrossRefGoogle ScholarPubMed
Pallast, EG, Schouten, EGDe Waart, FG, Fonk, HC, Doekes, G, von Blomberg, BM & Kok, FJ (1999) Effect of 50- and 100-mg vitamin E supplements on cellular immune function in noninstitutionalized elderly persons. Am J Clin Nutr 69, 1273–1281.CrossRefGoogle ScholarPubMed
Pawelec, G, Barnett, Y & Forsey, R (2002) T cells and aging, January 2002 update. Front Biosci 1, 1056–1283.CrossRefGoogle Scholar
Pawelec, G, Akbar, A, Caruso, C, Effros, R, Grubeck-Loebenstein, B & Wikby, A (2004) Is immunosenescence infectious?. Trends Immunol 25, 406–410.CrossRefGoogle ScholarPubMed
Pedersen, BK & Bruunsgaard, H (1995) How physical exercise influences the establishment of infections. Sports Med 19, 393–400.CrossRefGoogle ScholarPubMed
Peters, EM & Bateman, ED (1983) Ultramarathon running and URTI: an epidemiological survey. S A Med J 64, 582–584.Google Scholar
Peters, EM, Goetzsche, JM, Grobbelaar, B & Noakes, TD (1993) Vitamin C supplementation reduces the incidence of post-race symptoms of upper respiratory tract infection in ultramarathon runners. Am J, Clin Nutr 57, 170–174.CrossRefGoogle Scholar
Peters, EM, Goetzsche, JM, Joseph, LE & Noakes, TD (1996) Vitamin C as effective as combinations of anti-oxidant nutrients in reducing symptoms of upper respiratory tract infections in ultramarathon runners. S A J Sports Med 11, 23–27.Google Scholar
Petersen, EW & Pedersen, BK (2002) Exercise and immune function Nutrition and Immune Function 347 – 355 [Calder, PC, Fields, CJ, Gill, HS], Oxford: CABI PublishingCrossRefGoogle Scholar
Provinciali, M, Di Stefano, G & Fabris, N (1992) Optimization of cytotoxic assay by target cell retention of the fluorescent dye carboxyfluorescein diacetate (CFDA) and comparison with conventional 51 Cr release assay. J Immunol Methods 155, 19–24.CrossRefGoogle Scholar
Pyne, DB (1994) Regulation of neutrophil function during exercise. Sports Med 17, 245–258.CrossRefGoogle ScholarPubMed
Remick, DG (2002) Protein analysis and bioassays of cytokines and cytokine receptors. In Manual of Clinical Laboratory Immunology, 6th ed., pp. 320–337 [Rose, NR, Hamilton, B and Detrick, B, editors]. Washington, DC: ASM Press.Google Scholar
Renshaw, M, Rockwell, J, Englemann, C, Gerwirtz, A, Katz, J & Sambhara, S (2002) Cutting edge: impaired toll-like receptor expression and function in aging. J Immunol 169, 4697–4701.CrossRefGoogle ScholarPubMed
Robson, PJ, Blannin, AK, Walsh, NP, Castell, LM & Gleeson, M (1999) Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med 20, 128–135.Google ScholarPubMed
Roller, M, Rechkemmer, G & Watzl, B (2004) Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats. J Nutr 134, 153–156.CrossRefGoogle ScholarPubMed
Ronsen, O, Pedersen, BK, Oritsland, TR & Bahr, RKjeldsen-Kragh, J (2001) Leukocyte counts and lymphocyte responsiveness associated with repeated bouts of strenuous endurance exercise. J Appl Physiol 91, 425–434.CrossRefGoogle ScholarPubMed
Samartin, S & Chandra, RK (2001) Obesity, overnutrition and the immune system. Nutr Rev 21, 243–262.Google Scholar
Sapolsky, RM, Krey, LC & McEwen, BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 7, 284–301.CrossRefGoogle ScholarPubMed
Schellekens, PT, Roos, MT, De Wolf, F, Lange, JM & Miedema, F (1990) Low T-cell responsiveness to activation via CD3/TCR is a prognostic marker for acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus-1 (HIV-1)-infected men. J Clin Immunol 10, 121–127.CrossRefGoogle ScholarPubMed
Schnare, M, Barton, GM, Holt, AC, Takeda, K, Akira, S & Medzhitov, R (2001) Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2, 947–950.CrossRefGoogle ScholarPubMed
Scrimshaw, NS & SanGiovanni, JP (1997) Synergism of nutrition, infection and immunity: an overview. Am J Clin Nutr 66, 464S–477S.CrossRefGoogle Scholar
Shephard, RJ (1997) Physical Activity, Training and the Immune Response Carmel, IN: Cooper.Google Scholar
Shephard, RJ & Shek, PN (1999) Effects of exercise and training on natural killer cell counts and cytolytic activity: a meta-analysis. Sports Med 28, 177–195.CrossRefGoogle ScholarPubMed
Sherman, AR (1992) Zinc, copper and iron nutriture and immunity. J Nutr 122, 604–609.CrossRefGoogle ScholarPubMed
Sleijffers, A, Garssen, J, de Gruijl, FR, Boland, GJ, Van Hattum, J, Van Vloten, WA & Van Loveren, H (2001) Influence of ultraviolet B exposure on immune responses following hepatitis B vaccination in human volunteers. J Invest Dermatol 117, 1144–1150.CrossRefGoogle ScholarPubMed
Smith, DS, Helzner, EC, Nuttall, CE Jr, Collins, M, Rofman, BA, Ginsberg, D, Goswick, CB & Magner, A (1989) Failure of zinc gluconate in treatment of upper respiratory tract infections. Antimicrob Agents Chemother 33, 646–648.CrossRefGoogle ScholarPubMed
Smith, JK, Chi, DS, Krish, G, Reynolds, S & Cambron, G (1990) Effect of exercise on complement activity. Ann Allergy 65, 304–310.Google ScholarPubMed
Spirer, Z, Roifman, CM & Branski, D (1993) Pediatric Immunology. Pediatric and Adolescent Medicine, vol. 3. Basel: Karger.Google Scholar
Starkie, RL, Rolland, J, Angus, DJ, Anderson, MJ & Febbraio, M (2001) Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-α levels after prolonged running. Am J Physiol Cell Physiol 280, C769–C774.CrossRefGoogle Scholar
Steensberg, A, Van Hall, G, Osada, T, Sacchetti, M, Saltin, B & Pedersen, BK (2000) Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529, 237–242.CrossRefGoogle ScholarPubMed
Swain, P (2003) Wireless capsule: endoscopy. Gut 52, Suppl. 448–50.CrossRefGoogle ScholarPubMed
Tacket, CO, Binion, SB, Bostwick, E, Losonsky, G, Roy, MJ & Edelman, R (1992) Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. Am J Trop Med Hyg 47, 276–283.CrossRefGoogle ScholarPubMed
Tollerud, DJ, Morris Brown, L, Clark, JW, Neuland, CY, Mann, DL, Pankiw-Trost, LK & Blattner, WA (1991) Cryopreservation and long-term liquid nitrogen storage of peripheral blood mononuclear cells for flow cytometry analysis: effects on subsets proportions and fluorescence intensity. J Clin Lab Anal 5, 255–261.Google ScholarPubMed
Touloumi, G, Pantazis, N, Karafoulidou, A, Mandalaki, T, Goedert, JJ, Kostrikis, LG & Hatzakis, A (2004) Changes in T cell receptor excision DNA circle (TREC) levels in HIV type 1-infected subjects pre- and post-highly active antiretroviral therapy. AIDS Res Hum Retroviruses 20, 47–54.CrossRefGoogle Scholar
Turner, RB & Cetnarowski, WE (2000) Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 31, 1202–1208.CrossRefGoogle ScholarPubMed
Turner, RB, Riker, DK & Gangemi, JD (2000) Ineffectiveness of echinacea for prevention of experimental rhinovirus colds. Antimicrob Agents Chemother 44, 1708–1709.CrossRefGoogle ScholarPubMed
Van Loveren, H, Germolec, D, Koren, HS, Luster, MI, Nolan, C, Repetto, R, Smith, E, Vos, JG & Vogt, RF (1999) Report of the Bilthoven Symposium: Advancement of epidemiological studies in assessing the human health effects of immunotoxic agents in the environment and the workplace. Biomarkers 4, 135–157.CrossRefGoogle Scholar
Van Loveren, H, Van Amsterdam, JG, Vandebriel, RJ, Kimman, TG, Rumke, HC, Steerenberg, PS & Vos, JG (2001) Vaccine-induced antibody responses as parameters of the influence of endogenous and environmental factors. Environ Health Perspect 109, 757–764.CrossRefGoogle ScholarPubMed
Verde, TJ, Thomas, SG, Moore, RW, Shek, P & Shephard, RJ (1992) Immune responses and increased training of the elite athlete. J Appl Physiol 73, 1494–1499.CrossRefGoogle ScholarPubMed
Vignali, DA (2000) Multiplexed particle-based flow cytometric assays. J Immunol Methods 243, 243–255.CrossRefGoogle ScholarPubMed
Walker, LS (2004) CD4 + CD25 + Treg: divide and rule? Immunology 111, 129–137.CrossRefGoogle ScholarPubMed
Walrand, S, Moreau, K, Caldefie, F, Tridon, A, Chassagne, J, Portefaix, G, Cynober, L, Beaufrère, B, Vasson, M-P & Boirie, Y (2001) Specific and nonspecific immune responses to fasting and refeeding differ in young adult and elderly persons. Am J Clin Nutr 74, 670–678.CrossRefGoogle ScholarPubMed
Watzl, B & Watson, RR (1992) Role of alcohol abuse in nutritional immunosuppression. J Nut 122, 733–737.CrossRefGoogle ScholarPubMed
Weksler, ME (1995) Immune senescence: deficiency or dysregulation? Nutr Rev 53, Suppl., S1–S7.Google ScholarPubMed
Westermann, J & Pabst, R (1990) Lymphocyte subsets in the blood: a diagnostic window on the lymphoid system? Immunol Today 11, 406–410.CrossRefGoogle Scholar
Whiteside, TL, Bryant, J, Day, R & Herberman, RB (1990) Natural killer cytotoxicity in the diagnosis of immune dysfunction: criteria for a reproducible assay. J Clin Lab Anal 4, 102–114.CrossRefGoogle ScholarPubMed
Wiedermann, U, Kundi, M, Vollmann, U, Kollaritsch, H, Ebner, C & Wiedermann, G (2000) Different HBs antibody versus lymphoproliferative responses after application of a monovalent (hepatitis B) or combined (hepatitis A+hepatitis B) vaccine. Int Arch Allergy Immunol 123, 349–353.CrossRefGoogle ScholarPubMed
Wilder, RL (1998) Hormones, pregnancy, and autoimmune diseases. Ann N Y Acad Sci 840, 45–50.CrossRefGoogle ScholarPubMed
Wolf, R (2004) Essential Pediatric Allergy, Asthma and Immunology. New York: McGraw-Hill.Google Scholar
Woods, J, Lu, Q, Ceddia, MA & Lowder, T (2000) Special feature for the Olympics: effects of exercise on the immune system: exercise-induced modulation of macrophage function. Immunol Cell Biol 78, 545–553.Google ScholarPubMed
Yaqoob, P, Newsholme, EA & Calder, PC (1999) Comparison of cytokine production in cultures of whole human blood and purified mononuclear cells. Cytokine 11, 600–605.CrossRefGoogle ScholarPubMed
Ye, P & Kirshner, DE (2002) Measuring emigration of human thymocytes by T-cell receptor excision circles. Crit Rev Immunol 22, 483–497.CrossRefGoogle ScholarPubMed
Zaman, K, Baqui, AH, Yunus, M, Sack, RB, Chowdhury, HR & Black, RE (1997) Malnutrition, cell-mediated immune deficiency and acute upper respiratory infections in rural Bangladeshi children. Acta Paediatr 86, 923–927.CrossRefGoogle ScholarPubMed
Zeidel, A, Beilin, B, Yardeni, I, Mayburd, E, Smirnov, G & Bessler, H (2002) Immune response in asymptomatic smokers. Acta Anaesthesiol Scand 46, 959–964.CrossRefGoogle ScholarPubMed