Tumour necrosis factor (cachectin) and other cytokines in septic shock: a review of the literature

Abstract

The role of bacterial endotoxin in the pathogenesis of septic shock has been studied extensively. Endotoxin does not seem to exert most of its effects on the host directly, but rather it elicits the production of host factors that may in turn lead to shock and death. These factors, called cytokines, appear to be produced by cells of haematopoietic origin such as macrophages/monocytes, but can also be produced by other cells such as endothelium and fibroblasts. Three important cytokines associated with septic shock are tumour necrosis factor/cachectin (TNF), interleukin 1 (IL-1) and interleukin 6 (IL-6). The macrophage-derived TNF has been implicated as the most important host mediator in the pathogenesis of septic shock. TNF, alone or together with endotoxin or IL-1, is capable of inducing lethal shock and tissue injury resembling that of septic shock. It has also been suggested that IL-6 is involved in the pathogenesis of septic shock. The major biologic activities of IL-6 include B-cell differentiation and induction of the acute-phase proteins. In the present paper, reports addressing the current understanding of the biological, regulatory and clinical aspects of these cytokines are reviewed.