Cytokine Induced Stimulation of Endothelial Cells in Vitro

Abstract

Tumor necrosis factor/cachectin (TNF) is a central mediator of the host response (Beutler and Cerami 1986). It exerts endocrine, paracrine, and autocrine control of inflammatory responses (Sherry and Cerami 1988) and has been implicated in the pathogenesis of bacterial, parasitic, and viral infections and neoplastic disease. As one of the major secretory products of macrophages, TNF has been shown to play an important endocrine role in the pathogenesis of gram negative endotoxic shock (Beutler et al. 1985), cachexia associated with chronic disease (Tracey et al. 1988, Oliff et al. 1987), meningococcal septicemia (Waage et al. 1987), cerebral malaria (Grau et al. 1987), graft vs. host disease (Piguet et al. 1987), and cancer cachexia (Aderka et al. 1985, Balk-will et al. 1987). TNF can also be viewed as an autocrine immunomodulator, because it acts on the macrophage, the cell of principal origin (Philip and Epstein 1986). The view of TNF as a paracrine mediator stems from its local, tissue-specific effects. Endothelial cells respond to TNF (Pober 1988). They express specific binding sites for TNF (Nawroth et al. 1986) and respond with a dramatic change of their physiologic properties to TNF.