Endogenous Mechanisms Regulating TNF and IL-1 during Sepsis
In the past decade, it has become increasingly clear that proinflammatory cytokines play a prominent role in the pathophysiology of sepsis. Of these, tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) seem to be of particular importance. Administration of either TNF-α or IL-1 to experimental animals results in a syndrome that mimics sepsis, and therapy specifically directed against either cytokine protects against lethality in experimental sepsis and endotoxe- mia. In recent years, several endogenous mechanisms meant to protect the host against excessive activity of these highly potent cytokines have been identified. In this chapter, we will briefly discuss current knowledge of the roles of TNF and IL-1 in the pathogenesis of sepsis, and will provide an overview of endogenous mechanisms, that regulate the production and activities of TNF and IL-1.
KeywordsEndogenous Mechanism Tumor Necrosis Factor Level Experimental Endotoxemia Tumor Necrosis Factor Activity Tumor Necrosis Factor Receptor Type
Unable to display preview. Download preview PDF.
- 1.Van der Poll T, Lowry SF (1995) Tumor necrosis factor in sepsis: Mediator of multiple organ failure or essential part of host defense? Shock (in press)Google Scholar
- 21.Aiura K, Gelfand JA, Wakabayashi G, et al (1991) Interleukin-1 receptor antagonist blocks staphylococcal-induced shock in rabbits. Cytokine 3: 498–507Google Scholar
- 25.Van der Poll T, Jansen J, Levi M, ten Cate H, ten Cate JW, van Deventer SJH (1995) Regulation of interleukin-10 release by tumor necrosis factor in humans and chimpanzees. J Exp Med (in press)Google Scholar
- 27.Van der Poll T, Marchant A, Berman L, et al (1995) Endogenous interleukin-10 protects against death in septic peritonitis in mice. Surg Forum (in press)Google Scholar
- 37.Van der Poll T, Jansen J, Endert E, Sauerwein HP, van Deventer SJH (1994) Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin-6 production in human whole blood. Infect Immunol 62: 2046–2050Google Scholar
- 42.Van Zee KJ, Kohno T, Fischer E, Rock SC, Moldawer LL, Lowry SF (1992) Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor-α in vitro and in vivo. Proc Natl Acad Sci USA 89: 4845–4849PubMedCrossRefGoogle Scholar
- 43.Jansen J, van der Poll T, Levi M, et al (1995) Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotoxemia by an anti-tumor necrosis factor antibody. J Clin Immunol (in press)Google Scholar
- 45.Calvano E, Thompson WA, Coyle SM, et al (1993) Changes in monocyte and soluble tumor necrosis factor (TNF) receptors during endotoxemia or sepsis. Surg Forum 44: 114–116Google Scholar