Early cutaneous leishmaniasis patients infected with leishmania braziliensis express increased inflammatory responses after antimony therapy

Abstract

Background. Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb 5 ) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb 5 therapy, which leads to treatment failure. Methods. A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb 5 and to compare immunologic responses in ECL patients with CL and healthy subjects. Results. A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb 5 treatment. Although Sb 5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. Conclusions. The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy.