We are continuing our series on the immune system, inflammation related factors and potential drup targets that fall in the overlap of the immune and nervous system. Our last discussion covered the pro-inflammatory cytokines and their relevance to neuropathic pain. This week we will cover anti-inflammatory cytokines.
IL‐4 is released from activated mast cells and T cells and exerts anti-inflammatory effects by inhibiting release of IL‐1β, IL‐6, and TNF, promoting T cell differentiation into the anti‐inflammatory Th2 phenotype, and preventing macrophage and microglia activation. IL‐4 acts via two different heterodimers of IL‐4R. Using the spinal nerve ligation (SNL, Chung) model, pre‐treatment with IL‐4 delays onset of pain hypersensitivity and post‐treatment eliminates pain. These effects are associated with reductions in IL‐1β and microglial activation (1).
IL‐10 is released from activated lymphocytes, macrophages, and mast cells and is a potent anti-inflammatory cytokine, known to inhibit the release of IL‐1β, IL‐6, and TNF. IL‐10 functions through binding its heterodimeric IL‐10Rα/β complex. In several preclinical neuropathic pain models, intrathecal administration of IL‐10 prevents or reverses pain hypersensitivity. IL‐10 is thought to act via inhibition of pro‐inflammatory cytokine release and thus reduction in recruitment and activation of other immune and immune‐like glial cells (1).
TGF‐β is a pleiotropic, anti-inflammatory cytokine that acts via the TGF‐βRIII/RII heterodimeric complex. Intrathecal application of TGF‐β decreases development of pain hypersensitivity and eliminates existing pain in several preclinical models of neuropathic pain. These effects were associated with reductions in microglial proliferation, microglial and astrocytic activation, and neuronal expression of MCP‐1 (1).
Austin, PJ and Moalem-Taylor, G (2010) The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, iimmune-like glial cells and cytokines. Journal of Neuroimmunology, 229 (1-2):26.