Exacerbation of antigen-induced arthritis in IFN-gamma-deficient mice as a result of unrestricted IL-17 response
| Autor: | Rolf Bräuer, Mieczyslaw Gajda, Ingo M. Irmler |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
musculoskeletal diseases
Neutrophils Neutrophil granulocyte medicine.medical_treatment Immunology Arthritis Spleen Inflammation Antibodies Proinflammatory cytokine Interferon-gamma Mice Immune system Cell Movement Immunology and Allergy Medicine Animals Antigens Mice Knockout business.industry Interleukin-17 medicine.disease Arthritis Experimental Mice Inbred C57BL medicine.anatomical_structure Cytokine Acute Disease Antibody Formation Interleukin 17 Immunotherapy medicine.symptom business |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 179(9) |
| ISSN: | 0022-1767 |
| Popis: | Proinflammatory Th1 responses are believed to be involved in the induction and perpetuation of rheumatoid arthritis. However, the role of IFN-γ, the major cytokine produced by Th1 cells, is still incompletely defined. In the present study, we investigated the effects of IFN-γ deficiency (IFN-γ−/−) on the course of experimental murine Ag-induced arthritis (AIA). In the acute stage of disease, IFN-γ−/− AIA mice showed significantly increased inflammatory responses compared with wild-type C57BL/6 AIA mice, i.e., exacerbated joint swelling, increased delayed-type hypersensitivity reaction, and increased histopathological scores of arthritis. Intraarticular administration of exogenous IFN-γ at induction of AIA significantly suppressed these acute aggravation effects. Stimulated cells isolated from lymph nodes and spleen of IFN-γ−/− AIA mice showed increased production of IL-2, IL-4, IL-5, IL-6, but most prominently of IL-17. These elevations were paralleled by decreased humoral immune responses, with low serum levels of total and Ag-specific IgG (IgG1, IgG2ab, IgG2b, IgG3). At immunohistology, the knee joints of IFN-γ−/− AIA mice showed massive neutrophil granulocyte infiltration. Treatment with mAbs neutralizing IL-17 diminished the acute inflammation. In vitro, Th cell expansion and production of IL-17 upon restimulation were effectively and dose dependently inhibited by IFN-γ. These results clearly demonstrate that IFN-γ has anti-inflammatory properties during the initial phase of AIA, and indicate that IFN-γ deficiency exerts disease-promoting effects, preferentially via IL-17-modulated pathways. |
| Databáze: | OpenAIRE |
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