Reactive oxygen intermediates, nitrite and IFN-γ in Indian visceral leishmaniasis

Reactive oxygen intermediates (ROI), nitrite and interferon-gamma (IFN-gamma) production were investigated at different times during treatment in 10 patients with visceral leishmaniasis (VL). Hydrogen peroxide (H2O2), superoxide (O-2(-)) and IFN-gamma production by cultured monocytes from patients with active VL were significantly lower compared with the healthy controls. In contrast, nitrite levels in the supernatants from monocyte cultures of VL patients were comparable to healthy controls and increased significantly during antileishmanial therapy. On day 20 of treatment, a significant increase in the release of H2O2, O-2(-) and IFN-gamma was observed. However, at follow-up, 4 months after the end of treatment, the production of H2O2, O-2(-), IFN-gamma and nitrite had declined significantly. Thus, the impairment in hydrogen peroxide and superoxide production suggests that down-regulation of these mediators may be involved in the reduced killing of parasites by monocytes of active VL patients. Furthermore, the monocytes regained respiratory burst activity as the antileishmanial therapy progressed, suggesting that an immune-based mechanism is involved in successful drug therapy.