Parsons M S, Barrett L, Little C, Grant M D
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.
Endocr Metab Immune Disord Drug Targets. 2008 Sep;8(3):184-91. doi: 10.2174/187153008785700073.
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.
维持健康需要促炎介质和抗炎介质的影响之间保持动态平衡。虽然炎症在抵抗感染方面起着重要的保护作用，但不受控制的炎症会迅速致命，而无法消退的炎症会导致多种慢性疾病。使用细胞因子本身或细胞因子拮抗剂进行免疫治疗，由于疗效、安全性和成本等因素面临严格限制。通过生理调节途径重置促炎细胞因子和抗炎细胞因子之间的平衡的策略，可能会更成功地治疗慢性疾病的促炎成分。这种方法的一个新兴途径是利用细胞表面蛋白CD36与抗炎细胞因子白细胞介素-10（IL-10）之间的联系。增加CD36表达的药物和直接与CD36结合的药物具有抗炎特性，这可能与诱导IL-10直接相关。凋亡细胞的免疫抑制作用早在十多年前就有报道，此后在动物模型和多项临床试验中得到了验证。最近的一篇出版物表明，凋亡细胞诱导IL-10在很大程度上依赖于凋亡细胞与CD36之间的相互作用，CD36是单核细胞和巨噬细胞上凋亡细胞的受体。这在CD36参与和IL-10诱导之间提供了直接的机制联系，为使用CD36配体、增加CD36表达的药物或两者的组合来调节炎症、治疗甚至预防一系列重要的慢性疾病开辟了新的可能性。
