Role of Cytokines in Sepsis

Publisher Summary This chapter reviews the role of cytokines in the pathogenesis of sepsis. The various models for sepsis are also discussed, including the human models and animal models. The human model for sepsis most frequently studied is the experimental human endotoxemia. Cytokines usually have an auto- or paracrine-mode of action, although in some situations, in particular in sepsis, they exert effects at a distance from their site of production. Cytokines may be grouped based on their main biological effects: (1) those with main effects on the activation and proliferation of lymphocytes, (2) those with effects on hematopoiesis, (3) those with pro- and anti-inflammatory properties, and (4) those that orchestrate cell growth and differentiation during tissue repair. The notion that cytokines are involved in the pathogenesis of sepsis is based on several lines of evidence: (1) the intravenous administration of cytokines [TNF, IL1, and IL2] induces a septic shock-like syndrome in animals or humans, (2) the inhibition of the effects of some cytokines—by administration of neutralizing antibodies, soluble cytokine receptors, or receptor antagonists—attenuates sepsis in animal models, and (3) the administration of anti-inflammatory cytokines, such as IL10, mitigates severe sepsis in animals.