Increased nitric oxide production by airway cells of sensitized and challenged IL-10 knockout mice

The anti-inflammatory cytokine interleukin (IL)-10 suppresses inducible nitric oxide synthase (iNOS); therefore, NO production should increase in the absence of IL-10. Production of NO (as nitrite) by bronchoalveolar lavage cells of IL-10 knockout (^-/-) mice was assessed after ovalbumin sensitization and airway challenge (S/C) and was compared with the IL-10-sufficient, wild-type (WT) C57B6. Eosinophil recruitment occurred in S/C WT and IL-10^-/- mice, suggesting allergic airway inflammation. Alveolar macrophages (per g mouse) were unchanged (∼3×10⁴ cells) with the exception of a doubling in the S/C IL-10^-/- mice (∼6×10⁴ cells, P<0.05). NO production (per million cells) was doubled in cells from S/C IL-10^-/- (15.3 μM) mice compared with WT (7.6 μM, P<0.05). Inhibition of iNOS by L-N⁵-(l-iminoethyl)-ornithine reduced NO production in all S/C mice, confirming that the increase was a result of up-regulation of iNOS. We conclude that IL-10 is a critical cytokine regulating iNOS in murine airway cells and that its absence can lead to up-regulation of iNOS and development of allergic airway inflammation.