IL-10 inhibits cytokine production by activated macrophages

J Immunol. 1991 Dec 1;147(11):3815-22.


IL-10 inhibits the ability of macrophage but not B cell APC to stimulate cytokine synthesis by Th1 T cell clones. In this study we have examined the direct effects of IL-10 on both macrophage cell lines and normal peritoneal macrophages. LPS (or LPS and IFN-gamma)-induced production of IL-1, IL-6, and TNF-alpha proteins was significantly inhibited by IL-10 in two macrophage cell lines. Furthermore, IL-10 appears to be a more potent inhibitor of monokine synthesis than IL-4 when added at similar concentrations. LPS or LPS- and IFN-gamma-induced expression of IL-1 alpha, IL-6, or TNF-alpha mRNA was also inhibited by IL-10 as shown by semiquantitative polymerase chain reaction or Northern blot analysis. Inhibition of LPS-induced IL-6 secretion by IL-10 was less marked in FACS-purified peritoneal macrophages than in the macrophage cell lines. However, IL-6 production by peritoneal macrophages was enhanced by addition of anti-IL-10 antibodies, implying the presence in these cultures of endogenous IL-10, which results in an intrinsic reduction of monokine synthesis after LPS activation. Consistent with this proposal, LPS-stimulated peritoneal macrophages were shown to directly produce IL-10 detectable by ELISA. Furthermore, IFN-gamma was found to enhance IL-6 production by LPS-stimulated peritoneal macrophages, and this could be explained by its suppression of IL-10 production by this same population of cells. In addition to its effects on monokine synthesis, IL-10 also induces a significant change in morphology in IFN-gamma-stimulated peritoneal macrophages. The potent action of IL-10 on the macrophage, particularly at the level of monokine production, supports an important role for this cytokine not only in the regulation of T cell responses but also in acute inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / physiology
  • Base Sequence
  • Cell Line
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Gene Expression
  • In Vitro Techniques
  • Interleukin-10 / pharmacology*
  • Interleukin-4 / pharmacology
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides
  • Macrophage Activation
  • Macrophages / physiology*
  • Mice
  • Molecular Sequence Data
  • Oligonucleotides / chemistry
  • Peritoneal Cavity / cytology
  • RNA, Messenger / genetics
  • Tumor Necrosis Factor-alpha / genetics


  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • Oligonucleotides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4