EFFECT OF INTERFERON-GAMMA ON NITRIC-OXIDE HEMOGLOBIN PRODUCTION IN ENDOTOXIN-TREATED RATS AND ITS SYNERGISM WITH INTERLEUKIN-1 OR TUMOR-NECROSIS-FACTOR

We studied the in vivo effect of interferon-gamma (IFN-gamma) on nitri c oxide (NO) generation. ESR spectra of nitric oxide hemoglobin (HbNO) appeared after a lag time of 2h in the blood of rats treated with Esc herichia coli lipopolysaccharide (LPS). IFN-gamma enhanced LPS-induced HbNO formation in rats without modifying the time lag, although IFN-g amma alone did not include HbNO formation. The plasma nitrate concentr ation was approximately one order of magnitude higher than the HbNO co ncentration. On treatment with LPS alone, the amount of tumor necrosis factor (TNF) released decreased after 2 h. Simultaneous addition of I FN-gamma and LPS increased TNF release for at least 8 h. Interleukin 1 (IL-1) release was detected only at 2 h in both groups. We also inves tigated the in vivo interactions of these cytokines. TNF plus IL-1 ind uced the greatest HbNO generation, followed by TNF plus IFN-gamma, and then IL-1 plus IFN-gamma. These results suggest that increase of TNF release by IFN-gamma plays a key role in NO generation in LPS-treated rats.