Skip to main content Accessibility help
×
Home

Amelioration of murine cerebral malaria by dietary restriction

  • N. H. Hunt (a1), N. Manduci (a2) and C. M. Thumwood (a2)

Summary

CBA/T6 strain mice infected with Plasmodium berghei ANKA develop cerebral symptoms and die, with mononuclear cell attachment to the cerebral microvascular endothelium, petechial haemorrhages and breakdown of the blood–brain barrier, some 6–7 days post-inoculation. The effects of dietary restriction on this process were examined. Mice were fed ab libitum (Group 1) or their food was restricted to produce body weight loss of 1·0–2·0 % (Group 2), 2·5–3·5 % (Group 3), 4·0–6·5 % (Group 4) or 7·0–9·5 % (Group 5) relative to Group 1. Dietary restriction reduced deaths caused by cerebral malaria from 100% in Group 1 to 47% (Group 2), 43% (Group 3), 10% (Group 4) and 53% (Group 5). Restriction of food intake had no effect on (1) the progression of parasitaemia in infected mice (2) changes in haematocrit, spleen weight, total lymph node cell number or (3) peritoneal exudate cell number in either malaria-infected or uninfected mice. P. berghei ANKA infection did not significantly affect the proportion of lymph node leucocytes that were Thy-1+T cells or CD8+T cells, but did lead to significant increases in the CD4+ and B cell populations. Dietary restriction alone increased the lymph node CD4+cell population but did not affect the increase in B cells in malaria-infected mice. P. berghei ANKA infection and dietary restriction together did not lead to increased CD4+cell numbers in lymph node leucocytes. The in vitro proliferative response of isolated lymph node cells to concanavalin A or phorbol myristate acetate plus ionomycin was measured and found to be identical in all treatment groups. Plasma levels of tumour necrosis factor (TNF) increased from undetectable in uninfected mice or P. berghei ANKA-infected mice on days 1–6 post-inoculation to 21 ± 2 ng/ml on day 7 when cerebral symptoms were at their height and death was imminent. This increase in plasma TNF was substantially inhibited in those mice subjected to regimes of dietary restriction. There was a good correlation (r2 = 0·73) between plasma TNF level and percentage mortality in the 5 treatment groups. The results indicate that dietary status is an important factor in the outcome of murine cerebral malaria and perhaps, by extrapolation, in the human disease.

Copyright

References

Hide All
Beisel, W. R. (1982). Synergism and antagonism of parasitic disease and malnutrition. Review of Infectious Disease 4, 746–50.
Bendich, A., D'Apolito, P., Gabriel, E. & Machlin, L. J. (1984). Interaction of dietary vitamin C and vitamin E on guinea pig immune responses to mitogens. Journal of Nutrition 114, 1588–93.
Chan-Ling, T., Neill, A. L. & Hunt, N. H. (1992). Early microvascular changes in cerebral and non-cerebral malaria detected using retinal wholemounts. American Journal of Pathology 140, 1121–30.
Chaudhri, G., Clark, I. A., Hunt, N. H., Cowden, W. B. & Ceredig, R. (1986). Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation. Journal of Immunology 137, 2646–52.
Clark, I. A., Hunt, N. H. & Cowden, W. B. (1987). Immunopathology of malaria. In Immune Responses to Parasites (ed. Soulsby, E. J. L.), pp. 134. Baton Rouge: CRC Press.
Clark, I. A., Illschner, S., Macmicking, J. D. & Cowden, W. B. (1990). TNF and Plasmodium berghei ANKA-induced cerebral malaria. Immunology Letters 25, 195–8.
Das, B. S., Das, D. B., Satpathy, R. N., Patnaik, J. K. & Bose, T. K. (1988). Riboflavin deficiency and severity of malaria. European Journal of Clinical Nutrition 42, 277–83.
Eaton, J. W., Eckman, J. R., Berger, E. & Jacobs, H. S. (1976). Suppression of malaria infection by oxidant-sensitive host erythrocytes. Nature, London 264, 758–60.
Edington, G. M. (1954). Cerebral malaria in the Gold Coast African: four autopsy reports. Annual Review of Tropical Medicine and Parasitology 48, 300–6.
Edirisinghe, J. S., Fern, E. B. & Targett, G. A. T. (1981). The influence of dietary protein on the development of malaria. Annals of Tropical Paediatrics 1, 8791.
Endshaw, Y. & Assefa, D. (1990). Cerebral malaria: factors affecting outcome of treatment in suboptimal clinical setting. Journal of Tropical Medicine and Hygiene 93, 44–7.
Espevik, T. & Nissen-Meyer, J. (1986). A highly sensitive cell line, WEH1 164 clone 13, for measuring cytotoxic factor/tumour necrosis factor from human monocytes. Journal of Immunological Methods 95, 99105.
Grau, G. E., Piguet, P.-F., Engers, H. D., Louis, J. A., Vassalli, P. & Lambert, P. H. (1986). L3T4+ lymphocytes play a major role in the pathogenesis of murine cerebral malaria. Journal of Immunology 137, 2348–54.
Grau, G. E., Fajardo, L. F., Piguet, P.-F., Allet, B., Lambert, P.-H. & Vassalli, P. (1987). Tumour necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237, 1210–12.
Grau, G. E., Piguet, P.-F., Vassalli, P. & Lambert, P.-H. (1989). Tumor-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. Immunology Reviews 112, 4970.
Hunt, N. H., Thumwood, C. M., Clark, I. A. & Cowden, W. B. (1988). Are reactive oxygen species involved in cerebral malaria? In Free Radicals: Chemistry, Pathology and Medicine (ed. Rice-Evans, C. & Dormandy, T. L.), pp. 405414. London: Richelieu Press.
Levander, O. A., Ager, A. L. Jr, Morris, V. C. & May, R. G. (1989). Qinghaosu, dietary vitamin E, selenium, and cod-liver oil: effect on the susceptibility of mice to the malarial parasite Plasmodium yoelii. American Journal of Clinical Nutrition 50, 346–52.
Mackey, L. J., Hochmann, A., June, C. H., Contreras, C. E. & Lambert, P.-H. (1980). Immunopathological aspects of Plasmodium berghei infection in five strains of mice: II. Immunopathology of cerebral and other tissue lesions during the infection. Clinical and Experimental Immunology 42, 412–20.
Murray, M. J., Murray, A. B., Murray, N. J. & Murray, M. B. (1978). Diet and cerebral malaria: the effect of famine and refeeding. American Journal of Clinical Nutrition 31, 5761.
Neill, A. L. & Hunt, N. H. (1992). Pathology of fatal and resolving murine cerebral malaria. Parasitology 105, 165–75.
Osuntokun, B. O. (1983). Malaria and the nervous system. African Journal of Medical Science 12, 165–72.
Rest, J. R. (1982). Cerebral malaria in inbred mice. I. A new model and its pathology. Transactions of the Royal Society for Tropical Medicine and Hygiene 76, 410–15.
Tengerdy, R. P. (1990). The role of vitamin E in immune response and disease resistance. Annals of the New York Academy of Sciences 587, 2433.
Thumwood, C. M., Hunt, N. H., Clark, I. A. & Cowden, W. B. (1988). Breakdown of the blood-brain barrier in murine cerebral malaria. Parasitology 96, 579–89.
Thumwood, C. M., Hunt, N. H., Cowden, W. B. & Clark, I. A. (1989). Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. British Journal of Experimental Pathology 70, 293303.
Thurnham, D. I. (1985). Antimalarial effects of riboflavin deficiency. Lancet 1, 1310–11.
Yoshida, A. & Roth, E. F. (1987). Glucose-6-phosphate dehydrogenase of malaria parasite Plasmodium falciparum. Blood 69, 1528–30.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed