LAUSR

Mast cells (MCs) promote guest immune responses to parasites and play a critical role in allergic and inflammatory reactions. Once they have been activated, MCs release highly inflammatory compounds that can provoke serious pathologic signs that can lead to death. MCs generate a number of preformed, de novo synthesized compounds and inflammatory cytokine/chemokine synthesis in response to the high-affinity (Kd=10-10 M) immunoglobulin E receptor triggering. Circulating MC progenitors migrate into arterial intima and develop lesions, mediating inflammation. They are involved in several disorders, including metabolic diseases, such as type 2 diabetes mellitus, in which endothelial cells release several inflammatory compounds during acute and chronic vascular damage. Certain inflammatory cytokines, such as interleukin (IL)-1 and IL-33, not only are produced by MCs but also may activate them. These effects mediate systemic inflammatory responses in metabolic disorders. Proinflammatory cytokines, such as tumor necrosis factor, IL-33 and IL-6, secreted by MCs and other immune cells, contribute to insulin resistance by activating kinases. IL-37 (IL-1 family member 7), one of the latest cytokines discovered, binds the IL-18 receptor alpha (IL-18Rα) chain and suppresses innate and acquired immunity, with a therapeutic effect. It also inhibits cytokine levels, including IL-6, IL-18, IL-33, tumor necrosis factor and IL-1, and may improve insulin production and, therefore, the pathogenesis of diabetes, stroke and cardiovascular health. This describes a new concept of inhibition of and cure for inflammatory diseases. However, the safety, dosage and tolerability of this novel therapeutic agent, IL-37, still remains to be determined.