Strategies for use of IL-10 or its antagonists in human disease.
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.
O'Garra
Anne
A
Division of Immunoregulation, MRC National Institute for Medical Research, Mill Hill, London, UK. aogarra@nimr.mrc.ac.uk
Barrat
Franck J
FJ
Castro
Antonio G
AG
Vicari
Alain
A
Hawrylowicz
Catherine
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016233:Immunotherapy, Active; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D016753:Interleukin-10