Anti-inflammatory cytokines

Anti-inflammatory cytokines review

The anti-inflammatory cytokines are a series of immunoregulatory molecules that control the proinflammatory cytokines response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. Their physiologic role in inflammation and pathologic role in systemic inflammatory states are increasingly recognized. Major anti-inflammatory cytokines include interleukin (IL)-1 receptor antagonist, IL-4, IL-10, IL-11, and IL-13. Leukemia inhibitory factor, interferon-alpha, IL-6, and transforming growth factor (TGF)-β are categorized as either anti-inflammatory or proinflammatory cytokines, under various circumstances. Specific cytokine receptors for IL-1, TNF-α, and IL-18 also function as inhibitors for proinflammatory cytokines.

A dynamic and ever-shifting balance exists between proinflammatory cytokines and anti-inflammatory components (anti-inflammatory cytokines list) of the human immune system. The regulation of inflammation by these cytokines and cytokine inhibitors is complicated by the fact that the immune system has redundant pathways with multiple elements having similar physiologic effects. Furthermore, with the potential exception of interleukin (IL)-1 receptor antagonist (IL-1ra), all the anti-inflammatory cytokines have at least some proinflammatory properties as well.

The major anti-inflammatory cytokines and their specific roles in human disease has been described by many researchers. These inhibitory cytokines have already proven to be efficacious in a variety of clinical conditions marked by excess inflammation.

Anti-inflammatory cytokine: IL-10 with potent anti-inflammatory properties

Among all the anti-inflammatory cytokines, IL-10 is a cytokine with potent anti-inflammatory properties, repressing the expression of inflammatory cytokines such as TNF-α, IL-6 and IL-1 by activated macrophages. In addition, IL-10 can up-regulate endogenous anti-cytokines and down-regulate pro-inflammatory cytokine receptors. Thus, it can counter-regulate production and function of pro-inflammatory cytokines at multiple levels. Acute administration of IL-10 protein has been well-documented to suppress the development of spinally-mediated pain facilitation in diverse animal models such as peripheral neuritis, spinal cord excitotoxic injury, and peripheral nerve injury. Blocking spinal IL-10, on the other hand, has been found to prevent and even reverse established neuropathic pain behaviors. Recent clinical studies also indicate that low blood levels of IL-10 and another anti-inflammatory cytokine, IL-4, could be key to chronic pain since low concentrations of these two cytokines were found in patients with chronic widespread pain.

Anti-inflammatory cytokine: TGF-β is effective therapy for neuropathic pain

The family of TGF-β comprises 5 different isoforms (TGF-β1 to -β5). TGF-β1 is found in meninges, choroid plexus, and peripheral ganglia and nerves. It is known that TGF-β suppresses cytokine production by inhibiting macrophage and Th1 cell activity; counteracts IL-1, IL-2, IL-6, and TNF; and induces IL-1ra 6. Its mRNA is induced following axotomy and may be involved in a negative-feedback loop to limit the extent of glial activation. TGF-β1 also antagonizes nitric oxide production in macrophages. Nitric oxide has been strongly implicated in the final common pathway of neuropathic pain. It is expected that by its anti-cytokine action, TGF-β1 or agents that induce its activity may be effective therapy for neuropathic pain.

Anti-inflammatory cytokines related reference

1,Milligan ED, Sloane EM, Langer SJ, et al. Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10. Mol Pain 2005;1:9. [PubMed: 15813997]
2,Uceyler N, Valenza R, Stock M, et al. Reduced levels of anti-inflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum 2006;54:2656–2664. [PubMed: 16871547]
3, Wieseler-Frank J, Maier SF, Watkins LR. Glial activation and pathological pain. Neurochem Int 2004;45:389–395. [PubMed: 15145553]
4, Heijmans-Antonissen C, Wesseldijk F, Munnikes RJ, et al. Multiplex bead array assay for detection of 25 soluble cytokines in blister fluid of patients with complex regional pain syndrome type 1.Mediators Inflamm 2006;2006:28398. [PubMed: 16864900]
5, Roberts AB, Sporn MB. Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta). Growth Factors 1993;8:1–9. [PubMed: 8448037]

Cytokine molecules related

IFN Receptor

IL10 Family Receptor

TGF beta Family Receptor