IL-10 receptor dysfunction in macrophages during chronic inflammation

J Leukoc Biol. 2001 Oct;70(4):624-32.


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) alpha 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-alpha appeared to contribute to development of IL-10 hyporesponsiveness, because exposure of normal macrophages to TNF-alpha but not interferon-gamma reduced macrophage responsiveness to IL-10. Reverse transcriptase-PCR and flow cytometry demonstrated normal expression of the alpha and beta 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chronic Disease
  • Female
  • Inflammation / genetics
  • Inflammation / immunology*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / pharmacology
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Lung Diseases, Interstitial / genetics
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / virology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / biosynthesis
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-10
  • Retroviridae Infections / genetics
  • Retroviridae Infections / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / pharmacology


  • Interleukin-6
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Tumor Necrosis Factor-alpha
  • Interleukin-10