Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses

Daniel J Berg; Michael W Leach; Ralf Kühn; Klaus Rajewsky; Werner Müller; Natalie J Davidson; Donna Rennick

doi:10.1084/jem.182.1.99

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Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses

Journal article

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Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses

Daniel J Berg, Michael W Leach, Ralf Kühn, Klaus Rajewsky, Werner Müller, Natalie J Davidson and Donna Rennick

The Journal of experimental medicine, Vol.182(1), pp.99-108

07/01/1995

DOI: 10.1084/jem.182.1.99

PMCID: PMC2192105

PMID: 7790826

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Abstract

We have examined the role of endogenously produced interleukin (IL) 4 and IL-10 in the regulation of inflammatory and immune reactions in the skin. In these experiments, irritant and contact hypersensitivity (CH) responses were elicited in mice with targeted disruptions of the IL-4 (IL-4T) or IL-10 (IL-10T) gene. Our study showed that IL-4T and wild-type (wt) mice exhibited equivalent responses to the irritant croton oil. In contrast, the response of IL-10T mice challenged with croton oil was abnormally increased. When IL-10T mice were exposed to a higher dose of irritant, irreversible tissue damage occurred. By comparison, any treatment of wt mice with croton oil resulted in far less tissue damage and resolution of inflammation. Neutralizing antibody studies demonstrated that the necrosis that occurred in IL-10T mice was due to the overproduction of tumor necrosis factor. The anti-tumor necrosis factor antibody treatment of IL-10T mice did not significantly reduce the edema or the influx of inflammatory cells, suggesting that these changes were due to the uncontrolled production of other proinflammatory cytokines. T cell-dependent immune responses were also evaluated using the contact sensitizer oxazolone. The response of IL-4T mice did not differ from wt mice. In contrast, IL-10T mice mounted an exaggerated CH response, increased in both magnitude and duration as compared with wt mice. Based on these studies, we have concluded that IL-10, but not IL-4, is a natural suppressant of irritant responses and of CH, and it limits immunopathologic damage in the skin.

Details

Title: Subtitle: Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses
Creators: Daniel J Berg - Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
Michael W Leach - Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
Ralf Kühn - Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
Klaus Rajewsky - Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
Werner Müller - Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
Natalie J Davidson - Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
Donna Rennick - Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.182(1), pp.99-108
DOI: 10.1084/jem.182.1.99
PMID: 7790826
PMCID: PMC2192105
NLM abbreviation: J Exp Med
ISSN: 0022-1007
eISSN: 1540-9538
Language: English
Date published: 07/01/1995
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094400202771

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