[The role of cytokines and reactive oxygen species in the pathogenesis of sepsis]

Abstract

The role of cytokines and reactive oxygen species (ROS) in multiple and not fully explained pathogenesis of sepsis was presented. Close attention was paid to the contribution of inflammatory cytokines (TNF-alpha, IL-1, IL-6, IL-8) to the enhanced phagocyte-derived oxidative metabolism and the activation of respiratory burst. The pleiotropic interaction of these and the other cytokines creating so-called cytokine network was described, among other things in order to express the phagocytic and endothelial receptors. The significant role of polymorphonuclear leucocytes (PMNLs) and macrophages in the pathogenesis of sepsis was outlined, presenting not only their bactericidal activity but immunoregulatory effect connected with cytokine release as well. The significance of T cells cooperating with PMNLs was presented as well. The participation of antiinflammatory cytokines (IL-10, IL-13) and cytokine inhibitors e.g. soluble TNF receptor (sTNFR) and IL-1 receptor antagonist (IL-1 ra) was mentioned; all of them appear in septic patients and are thought to be natural regulators of immunological response in vivo. The key role of ROS generated by the activated phagocytes during sepsis has been outlined; it is proposed that the hypermetabolic response to sepsis results from enhanced ROS generation and so-called oxidant stress is a consequence of the imbalance between their generation and detoxification. The consequences of the action of oxygen free radicals resulting in lipid peroxidation followed by host auto-injury were also described. At the end a possibility of immunotherapy of sepsis connected with the application of pentoxifylline (PTXF) as TNF-alpha inhibitor was recommended to take into consideration.