Elevated levels of NO in both unchallenged and LPS-challenged C. parvum-primed mice are attributable to the activity of a cytokine-inducible isoform of iNOS

J Leukoc Biol. 1997 Jan;61(1):24-32. doi: 10.1002/jlb.61.1.24.


Elevated levels of nitric oxide (NO2-/NO3-) were detected in the serum of mice 3-7 days after priming with Corynebacterium parvum (Propionibacterium acnes). The serum NO2-/NO3- response was completely inhibited when C. parvum-primed (C. parrum) mice were treated with N(G)-monomethyl-L-arginine (L-NMMA) or aminoguanidine (AG) on days 6 and 7 post priming. The response was also inhibited when the mice were treated with interleukin-10 (IL-10) and the cytokine was most effective when given in multiple doses beginning on the day of priming. In contrast to L-NMMA and AG, IL-10 had no effect on the serum NO2-/NO3- response when administered to the mice on days 6 and 7 post priming. The inducible isoform of NOS (iNOS) appeared to be responsible for the elevated NO2-/NO3- response in C. parvum mice because iNOS transcripts were readily detected in their livers. Moreover, these transcripts as well as the circulating levels of NO2-/NO3- were dramatically reduced when the mice were treated with anti-tumor necrosis factor alpha (anti-TNF-alpha) or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibodies (mAbs) during the priming interval. There was a modest increase (less than twofold) in the serum NO2-/NO3- response following a lipopolysaccharide (LPS) challenge to C. parvum mice (C. parvum/LPS mice). LPS had a more dramatic stimulatory effect if the levels of NO2-/NO3- preexisting in C. parvum/LPS mice were reduced by treatment with L-NMMA, AG, or IL-10 before the challenge. Thus the levels of NO2-/NO3- that preexisted in C. parvum/LPS mice appeared to influence their ability to mount a NO2-/NO3- response subsequent to the LPS challenge. The NO2-/NO3- response did not contribute to lethality in C. parvum/LPS mice because anti-TNF-alpha and anti-IFN-gamma mAbs were protective but had no effect on serum NO2-/NO3- levels when administered to mice 24 h before the LPS challenge.

MeSH terms

  • Animals
  • Guanidines / pharmacology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / blood
  • Interferon-gamma / physiology*
  • Interleukin-10 / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / biosynthesis*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Nitrates / blood*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis*
  • Nitrites / blood*
  • Propionibacterium acnes*
  • Recombinant Proteins / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / physiology*
  • omega-N-Methylarginine / pharmacology


  • Guanidines
  • Isoenzymes
  • Lipopolysaccharides
  • Nitrates
  • Nitrites
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • omega-N-Methylarginine
  • Interferon-gamma
  • Nitric Oxide Synthase
  • pimagedine