Paradoxes and Pitfalls of Interleukin-33 in Atherosclerosis

ABSTRACT

Atherosclerosis is definitely considered as an inflammatory/immunopathological disease. The long-standing low-grade inflammation is focused on the components of the vessel wall. Initially, this inflammation was assumed to be driven by the pro-inflammatory Th1 cellular and cytokine immune responses. On the basis of accumulating knowledge, however, this view has been specified to include the Th17/Th1 axis which underlies most immunopathological diseases accompanied by sterile inflammation. On the other hand, an anti-inflammatory Th2 cellular and cytokine immune re-sponse attempts to dampen these unfavorable reactions which terminate in full-blown atherosclerosis. Interleukin-33, the novel member of the IL-1 cytokine superfamily, was suggested to take part in the anti-atherogenic response by mediating the Th1-to-Th2 switch of the immune reactions. However, IL-33 is a multifaceted mediator with both pro- and anti-inflammatory activities. IL-33 presents both an extracellular (cytokine-like) and a nuclear-bound (transcription factor-like) form, each of them performing distinct activities of their own. This review article summarizes latest data relevant to IL-33´s role in atherosclerosis, underscoring the paradoxes and pitfalls of laboratory findings and their extrapolation to live organisms including humans.

Keywords:

Interleukin -33, ST2 receptor, atherosclerosis, inflammation, lipid metabolism, gene transcription, Th1-to-Th2 transition.