Le rétrocontrôle négatif de l'inflammation: rôle des cytokines antiinflammatoires

Abstract

Transforming growth factor-β (TGFβ), interferon-α (IFNα), interleukin-4 (IL4), IL10 and IL13 have the capacity for inhibiting the production of inflammatory cvtokines such as IL1, IL6, tumour necrosis factor (TNFα), IL8 and the other chemokines. Consequently, these cytokines have been designated antimflammatory cytokines. In addition, they can counteract the proinflammatory activities of IL1 and TNF, such as tissue factor induction involved in coagulation, or the expression of adhesion molecules on the endothelial cell surface. Furthermore, IL4, IL10, IL13, TGFβ and IFNα can induce the production of IL1 receptor antagonists (IL1ra) which specifically limit the activity of IL1. The main natural inhibitors of TNF are the soluble TNF receptors, the release of which is enhanced during inflammation. Corticoids also repress the production of proinflammatory cytokines but do not affect or even enhance the production of antimflammatory cytokines. IL6, as the main inducer of acute phase protein synthesis, can be considered an antiinflammatory cytokine. However, all proinflammatory producing cells are not similarly sensitive to the effects of antiinflammatory cytokines. In addition, the nature and sequence of messages acting on the target cell may modify its reactivity to the negative signals delivered by the antiinflammatory cytokines. Finally, wide individual heterogeneity amplifies the diversity of the inflammatory responses. Thus, the world of cytokines is a complex one, and the nature of signals and of responding cells as well as the sequences of events are the unique characteristics of an inflammatory process induced by infectious and non-infectious stimuli.