Immune modulation by curcumin: The role of interleukin-10

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Abstract

Cytokines are small secreted proteins released by different types of cells with specific effects on cellular signaling and communication via binding to their receptors on the cell surface. IL-10 is known to be a pleiotropic and potent anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells including dendritic cells, macrophages, mast cells, natural killer cells, eosinophils, neutrophils, B cells, CD8+ T cells, and TH1, TH2, and TH17 and regulatory T cells. Both direct and indirect activation of the stress axis promotes IL-10 secretion. IL-10 deregulation plays a role in the development of a large number of inflammatory diseases such as neuropathic pain, Parkinson's disease, Alzheimer's disease, osteoarthritis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, type 1 diabetes, inflammatory bowel disease, and allergy. Curcumin is a natural anti-inflammatory compound able to induce the expression and production of IL-10 and enhancing its action on a large number of tissues. In vitro and in pre-clinical models curcumin is able to modulate the disease pathophysiology of conditions such as pain and neurodegenerative diseases, bowel inflammation, and allergy, but also of infections and cancer through its effect on IL-10 secretion. In humans, at least one part of the positive effects of curcumin on health could be related to its ability to enhance IL-10 -mediated effects.

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Radha K Maheshwari, Anoop Singh, Jaya P Gaddipati … (2006)

Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.

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Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones

MW Bond, DF Fiorentino, TR Mosmann (1989)

A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.

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Biology of interleukin-10.

Robert Sabat, Gerald Grütz, Katarzyna Warszawska … (2010)

Interleukin (IL)-10 is the most important cytokine with anti-inflammatory properties besides TGF-β and IL-35. It is produced by activated immune cells, in particular monocytes/macrophages and T cell subsets including Tr1, Treg, and Th1 cells. IL-10 acts through a transmembrane receptor complex, which is composed of IL-10R1 and IL-10R2, and regulates the functions of many different immune cells. In monocytes/macrophages, IL-10 diminishes the production of inflammatory mediators and inhibits antigen presentation, although it enhances their uptake of antigens. Additionally, IL-10 plays an important role in the biology of B cells and T cells. The special physiological relevance of this cytokine lies in the prevention and limitation of over-whelming specific and unspecific immune reactions and, in consequence, of tissue damage. At the same time, IL-10 strengthens the "scavenger"-function and contributes to induced tolerance. This review provides an overview about the cellular sources, molecular mechanisms, effects, and biological role of IL-10. Copyright © 2010 Elsevier Ltd. All rights reserved.