Harnessing CD36 to Rein in Inflammation

M.   S.   Parsons; L.      Barrett; C.      Little; M.   D.   Grant

doi:10.2174/187153008785700073

Abstract

Maintaining health requires a dynamic balance between the influence of pro-inflammatory and antiinflammatory mediators. While inflammation serves an important protective role against infection, unrestrained inflammation is acutely lethal and unresolved inflammation contributes to a broad range of chronic disorders. Immunotherapy with cytokines themselves or cytokine antagonists faces strict limitations due to efficacy, safety and cost. More successful treatment of the pro-inflammatory component of chronic disorders may emerge from strategies designed to reset the balance between pro and anti-inflammatory cytokines through physiological regulatory pathways. One emerging avenue for this approach is exploitation of the link between the cell surface protein CD36 and the anti-inflammatory cytokine interleukin- 10 (IL-10). Agents that increase CD36 expression and agents that directly bind to CD36 have anti-inflammatory properties that may directly relate to induction of IL-10. The immunosuppressive effects of apoptotic cells were first reported more than a decade ago and have since been tested in animal models and several clinical trials. A recent publication demonstrates that induction of IL-10 by apoptotic cells is largely dependent upon the interaction between apoptotic cells and CD36, the receptor on monocytes and macrophages for apoptotic cells. This provides a direct mechanistic link between CD36 engagement and IL-10 induction, opening up new possibilities for using CD36 ligands, agents that increase CD36 expression or a combination of both to modulate inflammation and treat, or even prevent, an important set of chronic disorders.

Keywords: Inflammation, interleukin-10, CD36, chronic disorders, apoptotic cells, PPAR-γ

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