Strategies for use of IL‐10 or its antagonists in human disease

Abstract

Summary: Interleukin‐10 (IL‐10) is a cytokine with broad anti‐inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen‐presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T‐helper 1 (Th1)‐type and Th2‐type responses. This review discusses the potential use of IL‐10 or agents that induce IL‐10 as potential anti‐inflammatory therapies in inflammatory diseases. Although IL‐10‐deficient mice develop colitis in the presence of normal gut flora and clear certain intracellular pathogens more efficiently, this is often accompanied by immunopathology, which can be lethal to the host. This reinforces the anti‐inflammatory properties of IL‐10, although it should be noted that as discussed below, IL‐10 can also promote B‐cell and other immune responses under particular settings. A penalty of its role to limit the immune and inflammatory responses to pathogens and prevent damage to the host is that high or dysregulated levels of IL‐10 may result in chronic infection. Thus, antagonists of IL‐10 show great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer. This article reviews basic published studies on IL‐10, which may lead to potential uses of IL‐10 or its antagonists in human disease.

Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a

“…It is secreted by various cell types like different T cell subsets, macrophages, dendritic cells (DC), B-cells, mast cells, and eosinophils. It mediates a plethora of immunoregulatory events such as maturation and activation of macrophages and DC, expression of MHC-II and B-7, activation of T cells, synthesis of cytokines, and antibody production (2,3). Also, dysregulation of IL-10 leads to various immunological diseases, such as cancer, rheumatoid arthritis, asthma, infectious disorders, etc.…”

“…Also, dysregulation of IL-10 leads to various immunological diseases, such as cancer, rheumatoid arthritis, asthma, infectious disorders, etc. (2). Therefore, it is likely that IL-10 expression is tightly regulated.…”

Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages

“…Neutralizing antibodies that inhibit the actions of particular proinflammatory cytokines, such as the anti-TNFα Humira, are having a major impact on the treatment of rheumatoid arthritis, Crohn's, and other inflammatory diseases, but these therapies are very expensive and only about half of the patients are good responders (22). The anti-inflammatory properties of IL-10 are being exploited in clinical trials to develop therapeutics for several inflammatory diseases, but results in the clinic using recombinant IL-10 have been disappointing, perhaps because elevated levels of IL-10 are required locally rather than systemically and/or because additional anti-inflammatory molecules are also needed (23,24). For these reasons, there is undiminished interest in developing orally available drugs to improve the treatment of chronic inflammatory and autoimmune diseases.…”

IL-10: Master Switch from Tumor-Promoting Inflammation to Antitumor Immunity

“…The IL-10-mediated suppression of IL-12/IL-23-dependent inflammation frequently is interpreted as a general immunosuppressive function. When LPS or other PRR ligands are injected directly into a tumor, the inflammatory response locally can result in sufficient tissue damage to reject a tumor, in particular if the inflammation is unrestricted, as in IL-10 knockout mice (16). This tumor rejection is primarily driven by inflammatory T cells and macrophages.…”