Suppression of monocyte function and differential regulation of IL-1 and IL-1ra by IL-4 contribute to resolution of experimental arthritis
| Autor: | J B Allen, H L Wong, G L Costa, M J Bienkowski, S M Wahl |
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| Rok vydání: | 1993 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 151:4344-4351 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | IL-4 has diverse effects on hematopoietic cells, including the ability to suppress certain mononuclear cell functions. To evaluate the effect of IL-4 on the evolution of acute and chronic arthritis, murine recombinant IL-4 was administered systemically to animals receiving an arthropathic dose of group A streptococcal cell wall fragments. Daily treatment with IL-4 had a minimal effect on the acute phase, but significantly suppressed the chronic, destructive phase. By 4 wk after initiation of disease, the articular index of IL-4-treated animals was reduced > 60% (articular index = 4 +/- 0.9) compared with the untreated rats (11.5 +/- 0.48, p < 0.001). A substantial decrease in the influx of inflammatory cells and virtual elimination of pannus and erosions occurred after IL-4 therapy. Associated with the reduced accumulation of mononuclear leukocytes was a decrease in their proinflammatory functions including cytokine production and reactive oxygen intermediate metabolism. These observations are consistent with the selective effects of IL-4 on phagocytic cell function demonstrated in vitro. Furthermore, IL-4 induced gene expression for IL-1ra, a protein that antagonizes the action of IL-1 by binding to the IL-1 receptor without agonist activity. Through an expanding spectrum of effects on monocyte-macrophage phenotypic and functional parameters, IL-4 is emerging as an important inhibitor of cell-mediated immune responses and pathogenic processes. |
| Databáze: | OpenAIRE |
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