Premium
IL‐10 receptor dysfunction in macrophages during chronic inflammation
Author(s) -
Avdiushko Rita,
Hongo David,
LakeBullock Helene,
Kaplan Alan,
Cohen Donald
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.4.624
Subject(s) - biology , immunology , macrophage , tumor necrosis factor alpha , inflammation , cytokine , immune system , bone marrow , interleukin 10 , lipopolysaccharide , retrovirus , receptor , in vitro , virus , biochemistry
The immunosuppressive activity of interleukin‐10 (IL‐10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected with the LP‐BM5 retrovirus had a reduced capacity to respond to IL‐10 in vitro. The ability of IL‐10 to inhibit lipopolysaccharide‐induced production of tumor necrosis factor (TNF) α and IL‐6 was significantly reduced in both alveolar and peritoneal macrophages from infected versus uninfected mice. IL‐10 hyporesponsiveness was not related to direct infection by the retrovirus, because bone marrow‐derived macrophages infected in vitro with LP‐BM5 were as responsive to IL‐10 as were uninfected bone marrow‐derived macrophages. TNF‐α appeared to contribute to development of IL‐10 hyporesponsiveness, because exposure of normal macrophages to TNF‐α but not interferon‐γ reduced macrophage responsiveness to IL‐10. Reverse transcriptase‐PCR and flow cytometry demonstrated normal expression of the α and β chains of the IL‐10 receptor in macrophages from infected mice, suggesting that IL‐10 hyporesponsiveness is not related to a change in receptor expression. The potential role of reduced IL‐10 responsiveness in the chronicity of inflammation in this and other diseases is discussed.