Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages

C. Bogdan, Y. Vodovotz, J. Paik, Q. Xie, C. Nathan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

215 Scopus citations


Nitric oxide (NO) contributes to the antitumor, antimicrobial, and immunosuppressive activity of macrophages. An inducible form of NO synthase (iNOS) is responsible for high output generation of nitric oxide by macrophages after stimulation with cytokines and/or lipopolysaccharide (LPS). In the present study, we demonstrate that interleukin 4 (IL-4) suppressed production of NO by primary mouse peritoneal macrophages exposed to IFN-γ with or without LPS, even while synergizing with IFN-γ to increase the secretion of TNF-α. Suppression of NO production was paralleled by decreases in iNOS enzyme activity and iNOS antigen. IL-4 did not inhibit induction of iNOS mRNA 4-6 h after exposure to IFN-γ, but strongly reduced iNOS mRNA at later times of stimulation (24-72 h), without increasing its turnover. The conditions for maximal suppression of iNOS expression by IL-4 and the mechanisms of suppression differed from those determined in parallel for transforming growth factor-β as described elsewhere. These results illustrate the diversity of phenotypes of macrophages deactivated by different cytokines, and demonstrate that IL-4 has the potential to reduce one component of the anti-tumor, antimicrobial, and immunosuppressive activities of macrophages.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalJournal of Leukocyte Biology
Issue number2
StatePublished - 1994
Externally publishedYes


  • cytokines
  • interferon-gamma
  • lipopolysaccharide


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