title: Harnessing CD36 to rein in inflammation.
abstract: Maintaining health requires a dynamic balance between the influence of pro-inflammatory and anti-inflammatory 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.
authors.affiliation: Immunology Program, Division of basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, NL, Canada A1B 3V6.
authors.forename: M S
authors.initials: MS
authors.lastname: Parsons
authors.forename: L
authors.initials: L
authors.lastname: Barrett
authors.forename: C
authors.initials: C
authors.lastname: Little
authors.forename: M D
authors.initials: MD
authors.lastname: Grant
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D018955:CD36 Antigens / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D016753:Interleukin-10 / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists
chemical_list: D000893:Anti-Inflammatory Agents; D018955:CD36 Antigens; D047495:PPAR gamma; D016753:Interleukin-10