Skip to main content Accessibility help
×
Home

Therapeutic potential of HMGB1-targeting agents in sepsis

  • Haichao Wang (a1) (a2), Shu Zhu (a1) (a2), Rongrong Zhou (a1) (a3), Wei Li (a1) (a2) and Andrew E. Sama (a1) (a2)...

Abstract

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. The inflammatory response is partly mediated by innate immune cells (such as macrophages, monocytes and neutrophils), which not only ingest and eliminate invading pathogens but also initiate an inflammatory response upon recognition of pathogen-associated molecular patterns (PAMPs). The prevailing theories of sepsis as a dysregulated inflammatory response, as manifested by excessive release of inflammatory mediators such as tumour necrosis factor and high-mobility group box 1 protein (HMGB1), are supported by extensive studies employing animal models of sepsis. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of experimental sepsis, and discuss the therapeutic potential of several HMGB1-targeting agents (including neutralising antibodies and steroid-like tanshinones) in experimental sepsis.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Therapeutic potential of HMGB1-targeting agents in sepsis
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Therapeutic potential of HMGB1-targeting agents in sepsis
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Therapeutic potential of HMGB1-targeting agents in sepsis
      Available formats
      ×

Copyright

Corresponding author

*Corresponding author: Haichao Wang, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA. Tel: +1 516 562 2823; Fax: +1 516 562 1022; E-mail: hwang@nshs.edu

References

Hide All
1Serhan, C.N. and Savill, J. (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6, 1191-1197
2Dellinger, R.P. et al. (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36, 296-327
3Luster, A.D., Alon, R., and von Andrian, U.H. (2005) Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 6, 1182-1190
4Scapini, P. et al. (2000) The neutrophil as a cellular source of chemokines. Immunol Rev 177, 195-203
5Liles, W.C. (2001) Immunomodulatory approaches to augment phagocyte-mediated host defense for treatment of infectious diseases. Semin Respir Infect 16, 11-17
6Mosser, D.M. (1999) Receptors on phagocytic cells involved in microbial recognition. Immunol Ser 60, 99-114
7Wu, Y., Tibrewal, N. and Birge, R.B. (2006) Phosphatidylserine recognition by phagocytes: a view to a kill. Trends Cell Biol 16, 189-197
8Hemmi, H. et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745
9Krieg, A.M. (2002) CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 20, 709-760
10Brightbill, H.D. et al. (1999) Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285, 732-736
11Poltorak, A. et al. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088
12Akira, S. and Takeda, K. (2004) Toll-like receptor signalling. Nat Rev Immunol 4, 499-511
13Baggiolini, M. and Loetscher, P. (2000) Chemokines in inflammation and immunity. Immunol Today 21, 418-420
14Balkwill, F. (1988) Cytokines-soluble factors in immune responses. Curr Opin Immunol 1, 241-249
15Wichterman, K.A., Baue, A.E. and Chaudry, I.H. (1980) Sepsis and septic shock–a review of laboratory models and a proposal. J Surg Res 29, 189-201
16Lowenstein, C.J., Dinerman, J.L. and Snyder, S.H. (1994) Nitric oxide: a physiologic messenger. Ann Intern Med 120, 227-237
17Tracey, K.J. et al. (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330, 662-664
18Dinarello, C.A. and Thompson, R.C. (1991) Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today 12, 404-410
19Block, M.I. et al. (1993) Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia. J Exp Med 178, 1085-1090
20Heinzel, F.P. (1990) The role of IFN-gamma in the pathology of experimental endotoxemia. J Immunol 145, 2920-2924
21Bernhagen, J. et al. (1993) MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 365, 756-759
22Calandra, T. et al. (2000) Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat Med 6, 164-170
23Bozza, M. et al. (1999) Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med 189, 341-346
24Davis, C.E. et al. (1969) Prevention of death from endotoxin with antisera. I. The risk of fatal anaphylaxis to endotoxin. J Immunol 102, 563-572
25Knudsen, P.J. et al. (1986) Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J Immunol 137, 3189-3194
26Oswald, I.P. et al. (1992) Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation. Proc Natl Acad Sci U S A 89, 8676-8680
27Bogdan, C., Vodovotz, Y. and Nathan, C. (1991) Macrophage deactivation by interleukin 10. J Exp Med 174, 1549-1555
28Tsunawaki, S. et al. (1988) Deactivation of macrophages by transforming growth factor-beta. Nature 334, 260-262
29Miller-Graziano, C.L. et al. (1991) Role of elevated monocyte transforming growth factor beta (TGF beta) production in posttrauma immunosuppression. J Clin Immunol 11, 95-102
30Zhang, M. et al. (1997) Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response. J Exp Med 185, 1759-1768
31Zhang, M. et al. (1999) Spermine inhibition of monocyte activation and inflammation. Mol Med 5, 595-605
32Wang, H. et al. (1998) Fetuin (alpha2-HS-glycoprotein) opsonizes cationic macrophagedeactivating molecules. Proc Natl Acad Sci U S A 95, 14429-14434
33Zhang, M., Wang, H. and Tracey, K.J. (2000) Regulation of macrophage activation and inflammation by spermine: a new chapter in an old story. Crit Care Med 28, N60-N66
34Borovikova, L.V. et al. (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458-462
35Lefering, R. and Neugebauer, E.A. (1995) Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med 23, 1294-1303
36Annane, D. et al. (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288, 862-871
37Sprung, C.L. et al. (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358, 111-124
38Bernard, G.R. et al. (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344, 699-709
39Warren, B.L. et al. (2001) Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 286, 1869-1878
40Abraham, E. et al. (2003) Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 290, 238-247
41Rivers, E. et al. (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345, 1368-1377
42Sama, A.E. et al. (2004) Bench to bedside: HMGB1-a novel proinflammatory cytokine and potential therapeutic target for septic patients in the emergency department. Acad Emerg Med 11, 867-873
43Russell, J.A. et al. (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358, 877-887
44van den Berghe, G. et al. (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345, 1359-1367
45van den Berghe, G. et al. (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354, 449-461
46Brunkhorst, F.M. et al. (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358, 125-139
47Chen, G. et al. (2005) Suppression of HMGB1 release by stearoyl lysophosphatidylcholine:an additional mechanism for its therapeutic effects in experimental sepsis. J Lipid Res 46, 623-627
48Bonaldi, T. et al. (2003) Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 22, 5551-5560
49Bustin, M. (2002) At the crossroads of necrosis and apoptosis: signaling to multiple cellular targets by HMGB1. Sci STKE 2002, E39
50Oppenheim, J.J. and Yang, D. (2005) Alarmins: chemotactic activators of immune responses. Curr Opin Immunol 17, 359-365
51Wang, H. et al. (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248-251
52Ivanov, S. (2007) A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 110, 1970-1981
53Rendon-Mitchell, B. et al. (2003) IFN-gamma Induces High Mobility Group Box 1 Protein Release Partly Through a TNF-Dependent Mechanism. J Immunol 170, 3890-3897
54Tang, D. et al. (2007) Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1. J Leukoc Biol 81, 741-747
55Gardella, S. et al. (2002) The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep 3, 955-1001
56Scaffidi, P., Misteli, T. and Bianchi, M.E. (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191-195
57Chu, J.J. and Ng, M.L. (2003) The mechanism of cell death during West Nile virus infection is dependent on initial infectious dose. J Gen Virol 84, 3305-3314
58Joseph, T. et al. (2004) Mechanism of cell death during infectious salmon anemia virus infection is cell type-specific. J Gen Virol 85, 3027-3036
59Chen, L.C. et al. (2008) Dengue virus infection induces passive release of high mobility group box 1 protein by epithelial cells. J Infect 56, 143-150
60Wang, H. et al. (2006) Potential role of high mobility group box 1 in viral infectious diseases. Viral Immunol 19, 3-9
61Fages, C. et al. (2000) Regulation of cell migration by amphoterin. J Cell Sci 113 (Pt 4), 611-620
62Degryse, B. et al. (2001) The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. J Cell Biol 152, 1197-1206
63Huttunen, H.J. et al. (2002) Receptor for advanced glycation end products-binding COOH-terminal motif of amphoterin inhibits invasive migration and metastasis. Cancer Res 62, 4805-4811
64Palumbo, R. et al. (2004) Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation. J Cell Biol 164, 441-449
65Palumbo, R. et al. (2007) Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-kappaB activation. J Cell Biol 179, 33-40
66Rouhiainen, A. et al. (2004) Regulation of monocyte migration by amphoterin (HMGB1). Blood 104, 1174-1182
67Yang, D. et al. (2007) High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin. J Leukoc Biol 81, 59-66
68Dumitriu, I.E. et al. (2007) The secretion of HMGB1 is required for the migration of maturing dendritic cells. J Leukoc Biol 81, 84-91
69Orlova, V.V. et al. (2007) A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin. EMBO J 26, 1129-1139
70Degryse, B. and de Virgilio, M. (2003) The nuclear protein HMGB1, a new kind of chemokine? FEBS Lett 553, 11-17
71Tian, J. et al. (2007) Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8, 487-496
72Silva, E. et al. (2007) HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury. Intensive Care Med 33, 1829-1839
73Park, J.S. et al. (2004) Involvement of TLR 2 and TLR 4 in cellular activation by high mobility group box 1 protein (HMGB1). J Biol Chem 279, 7370-7377
74Yu, M. et al. (2006) HMGB1 signals through Toll-like Receptor (TLR) 4 and TLR2. Shock 26, 174-179
75Park, J.S. et al. (2006) High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol 290, C917-C924
76Kokkola, R. et al. (2005) RAGE is the Major Receptor for the Proinflammatory Activity of HMGB1 in Rodent Macrophages. Scand J Immunol 61, 1-9
77Pedrazzi, M. et al. (2007) Selective proinflammatory activation of astrocytes by high-mobility group box 1 protein signaling. J Immunol 179, 8525-8532
78Fiuza, C. et al. (2003) Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood 101, 2652-2660
79Treutiger, C.J. et al. (2003) High mobility group 1 B-box mediates activation of human endothelium. J Intern Med 254, 375-385
80Yang, H. et al. (2004) Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A 101, 296-301
81Kokkola, R. et al. (2003) Successful treatment of collagen-induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity. Arthritis Rheum 48, 2052-2058
82Li, J. et al. (2003) Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol Med 9, 37-45
83Messmer, D. et al. (2004) High mobility group box protein 1: an endogenous signal for dendritic cell maturation and Th1 polarization. J Immunol 173, 307-313
84Li, W. et al. (2007) A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1. PLoS ONE 2, e1153
85Andersson, U. et al. (2000) High Mobility Group 1 Protein (HMG-1) Stimulates Proinflammatory Cytokine Synthesis in Human Monocytes. J Exp Med 192, 565-570
86Agnello, D. et al. (2002) HMGB1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion. Cytokine 18, 231-236
87Pedrazzi, M. et al. (2006) Stimulation of excitatory amino acid release from adult mouse brain glia subcellular particles by high mobility group box 1 protein. J. Neurochem 99, 827-838
88O'Connor, K.A. et al. (2003) Further characterization of high mobility group box 1 (HMGB1) as a proinflammatory cytokine: central nervous system effects. Cytokine 24, 254-265
89Liu, K. et al. (2007) Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats. FASEB J 21, 3904-3916
90Abraham, E. et al. (2000) HMG-1 as a mediator of acute lung inflammation. J Immunol 165, 2950-2954
91Ueno, H. et al. (2004) Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med 170, 1310-1316
92Lin, X. et al. (2005) {alpha}-Chemokine receptor blockade reduces high mobility group box 1 protein-induced lung inflammation and injury and improves survival in sepsis. Am J Physiol Lung Cell Mol Physiol 289, L583-L590
93Liu, G. et al. (2008) High mobility group protein-1 Inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine. J Immunol 181, 4240-4246
94Bell, C.W. et al. (2006) The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol Cell Physiol 291, C1318-1325
95Qin, S. et al. (2006) Role of HMGB1 in apoptosis-mediated sepsis lethality. J Exp Med 203, 1637-1642
96Wang, H. et al. (2001) HMGB1 as a Late Mediator of Lethal Systemic Inflammation. Am J Respir Crit Care Med 164, 1768-1773
97Suda, K. et al. (2006) Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis. World J Surg 30, 1755-1762
98Sappington, P.L. et al. (2002) HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice. Gastroenterology 123, 790-802
99Tsung, A. et al. (2005) The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med 201, 1135-1143
100Oozawa, A. et al. (2008) Effects of HMGB1 on ischemia-reperfusion injury in the rat heart. Circ J 72, 1178-1184
101Wu, H. et al. (2007) TLR4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest 117, 2847-2859
102Liu, K. et al. (2007) Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats. FASEB J 21, 3904-3916
103Andrassy, M. et al. (2008) High-mobility group box-1 in ischemia-reperfusion injury of the heart. Circulation 117, 3216-3226
104Ogawa, E.N. et al. (2006) Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury. Am J Respir Crit Care Med 174, 400-407
105Sawa, H. et al. (2006) Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis. World J Gastroenterol 12, 7666-7670
106Yang, R. et al. (2006) Anti-HMGB1 neutralizing antibody ameliorates gut barrier dysfunction and improves survival after hemorrhagic shock. Mol Med 12, 105-114
107Li, W., Sama, A.E. and Wang, H. (2006) Role of HMGB1 in cardiovascular diseases. Curr Opin Pharmacol 6, 130-135
108Czermak, B.J. et al. (1999) Protective effects of C5a blockade in sepsis. Nat Med 5, 788-792
109Riedemann, N.C. et al. (2002) Increased C5a receptor expression in sepsis. J Clin Invest 110, 101-108
110Rittirsch, D. et al. (2008) Functional roles for C5a receptors in sepsis. Nat Med 14, 551-557
111Hagiwara, S. et al. (2008) High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats. Intensive Care Med 34, 361-367
112Abeyama, K. (2005) The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism. J Clin Invest 115, 1267-1274
113Hagiwara, S. et al. (2008) Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats. Crit Care 12, R43
114Hagiwara, S. et al. (2008) High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis. Intensive Care Med 34, 1812-1819
115Urbonaviciute, V. et al. (2007) Factors masking HMGB1 in human serum and plasma. J Leukoc Biol 81, 67-74
116Hagiwara, S. et al. (2008) Effects of hyperglycemia and insulin therapy on high mobility group box 1 in endotoxin-induced acute lung injury in a rat model. Crit Care Med 36, 2407-2413
117Wang, H. et al. (2008) Hyperglycemia aggravates endotoxin-induced high mobility group box 1 protein release: yet another reason not to be too sweet. Crit Care Med 36, 2475-2476
118Chorny, A. and Delgado, M. (2008) Neuropeptides rescue mice from lethal sepsis by down-regulating secretion of the late-acting inflammatory mediator high mobility group box 1. Am J Pathol 172, 1297-1307
119Tang, Y. et al. (2008) PACAP inhibit the release and cytokine activity of HMGB1 and improve the survival during lethal endotoxemia. Int Immunopharmacol 8, 1646-1651
120Wu, R. et al. (2007) Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats. Am J Respir Crit Care Med 176, 805-813
121Wu, R. et al. (2007) Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve. Ann Surg 245, 480-486
122Chorny, A. et al. (2008) Ghrelin protects against experimental sepsis by inhibiting high-mobility group box 1 release and by killing bacteria. J Immunol 180, 8369-8377
123Tracey, K.J. (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 117, 289-296
124Wang, H. et al. (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421, 384-388
125Huston, J.M. et al. (2006) Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med 203, 1623-1628
126Huston, J.M. et al. (2007) Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med 35, 2762-2768
127Wang, H. (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10, 1216-1221
128Pavlov, V.A. et al. (2007) Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med 35, 1139-1144
129Yan, J.J. et al. (2004) Therapeutic effects of lysophosphatidylcholine in experimental sepsis. Nat Med 10, 161-167
130Wang, H., Czura, C.J. and Tracey, K.J. (2004) Lipid unites disparate syndromes of sepsis. Nat Med 10, 124-125
131Fink, M.P. (2007) Ethyl pyruvate: a novel treatment for sepsis. Curr Drug Targets 8, 515-518
132Ulloa, L. et al. (2002) Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci U S A 99, 12351-12356
133Zhu, S. et al. (2008) Caging a beast in the inflammation arena: use of Chinese medicinal herbs to inhibit a late mediator of lethal sepsis, HMGB1. Int J Clin Exp Med 1, 64-79
134Wang, H. et al. (2006) The aqueous extract of a popular herbal nutrient supplement, Angelica sinensis, protects mice against lethal endotoxemia and sepsis. J Nutr 136, 360-365
135Li, W. et al. (2007) A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. J Immunol 178, 3856-3864
136Piersen, C.E. (2003) Phytoestrogens in botanical dietary supplements: implications for cancer. Integr Cancer Ther 2, 120-138
137Osuchowski, M.F. et al. (2006) Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol 177, 1967-1974
138Ji, X.Y., Tan, B.K. and Zhu, Y.Z. (2000) Salvia miltiorrhiza and ischemic diseases. Acta Pharmacol Sin 21, 1089-1094
139Cheng, T.O. (2007) Cardiovascular effects of Danshen. Int J Cardiol 121, 9-22
140Beutler, B., Milsark, I.W. and Cerami, A.C. (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229, 869-871
141Ziegler, E.J. et al. (1991) Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med 324, 429-436
142Ziegler, E.J. et al. (1982) Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 307, 1225-1230
143Abraham, E. et al. (1995) Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA 273, 934-941
144Cohen, J. (1999) Adjunctive therapy in sepsis: a critical analysis of the clinical trial programme. Br Med Bull 55, 212-225
145Feldmann, M. and Maini, R.N. (2001) Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol 19, 163-196
146Wang, H., Yang, H. and Tracey, K.J. (2004) Extracellular role of HMGB1 in inflammation and sepsis. J Intern Med 255, 320-331
147Lotze, M.T. and Tracey, K.J. (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5, 331-342
148Sunden-Cullberg, J. et al. (2005) Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Crit Care Med 33, 564-573
149Angus, D.C. et al. (2007) Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis. Crit Care Med 35, 1061-1067
150Sha, Y. et al. (2008) HMGB1 develops enhanced proinflammatory activity by binding to cytokines. J Immunol 180, 2531-2537
151Kazama, H. et al. (2008) Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29, 21-32
152Tzeng, H.P. et al. (2008) Negative inotropic effects of high-mobility group box 1 protein in isolated contracting cardiac myocytes. Am J Physiol Heart Circ Physiol 294, H1490-H1496 antiserum to a mutant Escherichia coli. N Engl J Med 307, 1225-1230
Chadwick, D.J. and Goode, J., eds (2007) Novartis Foundation Symposium 280: Sepsis – New Insights. New Therapies, John Wiley & Sons, New York, USA

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