Lipopolysaccharide inhibits the late-phase response to allergen by altering nitric oxide synthase activity and interleukin-10

We have previously shown that exposure of sensitized animals to lipopolysaccharide (LPS) 18 h after ovalbumin (OVA) challenge inhibits late-airway response (LAR), Using relatively selective nitric oxide synthase (NOS) inhibitors we have shown that LPS upregulates inducible NOS (iNOS) and downregulates constitutive NOS (cNOS) activity. In this study we set out to quantitate NOS isoenzyme activity in lung homogenates and to measure ex vivo interleukin (IL)-10 in tracheal explants of naive or sensitized and OVA-challenged rats exposed to LPS. iNOS activity was increased and cNOS activity reduced 6 h after LPS exposure in naive animals (n = 6, P < 0.001) and at 18 (n = 5, P < 0.001) or 24 (n = 5, P < 0.001) h after OVA challenge in sensitized animals. LPS exposure 18 h after OVA challenge in sensitized animals reversed OVA-induced changes in NOS isoenzyme activities (n = 5, P < 0.001). In naive animals IL-10 was increased 1 h after LPS exposure (n = 5, P < 0.001), peaked at 3 h (n = 9, P < 0.001), and remained elevated above baseline at 18 h (n = 11, P < 0.05). In sensitized animals, IL-10 was not increased until 18 h after OVA challenge (n = 11, P < 0.001). Due to the rapid IL-10 increase in naive animals the released IL-10 is likely to be preformed; however, in sensitized animals the results are consistent with de novo production of IL-10. In the sensitized and OVA-challenged group, exposure to LPS 18 h after OVA produced a 3-fold increase in IL-10 at 3 h after LPS exposure (n = 5, P < 0.001). The time course and kinetics of IL-10 release in those animals was similar to that seen in naive rats. These results support our previous conclusions on the basis of in vivo studies using isoenzyme inhibitors and have shown LPS to be able to reverse OVA-induced changes in NOS isoenzyme activities during an established LAR. LPS-induced release of IL-10 is thought to play an important immunomodulatory role in this model.