Authors: Ogawa, Yoshiko; Duru, Enrico A.; Ameredes, Bill T.

Source: Current Molecular Medicine, Volume 8, Number 5, August 2008 , pp. 437-445(9)

Publisher: Bentham Science Publishers

Abstract:

IL-10 can be considered an important agent in the resolution of inflammation. Originally named “cytokine synthesis inhibitory factor” for its ability to inhibit IFN-γ and IL-2 production in Th2 cells, it is secreted by monocytes, macrophages, mast cells, T and B lymphocytes, and dendritic cells (DCs). IL-10 production and release by monocytic cells in response to allergic challenge is upregulated by TNF-α, and by negative feedback regulation of itself. However, it is also secreted by T regulatory cells (Tregs), under the control of IL- 2. Importantly in the context of asthma, IL-10 inhibits eosinophilia, by suppression of IL-5 and GM-CSF, by direct effects on eosinophil apoptosis, and effects on cell proliferation through down-regulation of IL-1. A number of its cytokine suppressive characteristics are now thought to occur through its upregulation of suppressor of cytokine signaling (SOCS)-3. IL-10 is also a suppressor of nitric oxide (NO) production, which may have ramifications for its role in airway inflammatory diseases. Initial clinical trials have demonstrated relative safety and few clinically adverse events at doses of recombinant human IL-10 below 50 μg/kg, with mixed success in treatment of patients with inflammatory bowel disease and psoriasis. However, both steroid therapy and allergen specific immunotherapy are known to elevate endogenous IL-10 levels, which may account for their efficacy, suggesting that further study of IL-10 as a target for treatment of airway inflammatory diseases such as asthma and COPD is warranted.

Keywords: Allergy; antigen-presenting cells; asthma; T regulatory cells

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156652408785160907

Publication date: 2008-08-01

More about this publication?

• Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.

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