Antigen-triggered interferon-γ and interleukin-10 pattern in cured mucosal leishmaniasis patients is shaped during the active phase of disease.

An exacerbated type 1 response to leishmanial antigens is the basis of tissue destruction observed in mucosal leishmaniasis ( ML). After therapy, a persistent production of high levels of inflammatory cytokines can confer a poor prognosis. Herein we investigated whether the clinical conditions defined during the active phase of ML affect the magnitude of long-term anti- Leishmania immune response. Twenty clinically cured ML cases were studied. Peripheral blood mononuclear cells ( PBMC) were cultured with L. braziliensis antigens (Lb- Ag), Toxoplasma gondii antigens (Tg- Ag), concanavalin- A ( Con- A) or medium alone, and the lymphocyte proliferative response and cytokine secretion were quantified. Medical records were reviewed for Montenegro skin test ( MST) during diagnosis, duration of ML disease or time elapsed after clinical cure. The duration of disease was correlated positively with MST ( r = 0·61). Lb- Ag induced interferon ( IFN)-γ was correlated positively with duration of illness ( r = 0·69) as well as the frequency of secreting cells [enzyme-linked immunospot ( ELISPOT)] assay. No association was observed for Tg- Ag or Con-A. Disease duration was correlated negatively with interleukin ( IL)-10 production ( r = −0·76). Moreover, a negative correlation between length of time after clinical cure and TNF levels ( r = −0·94) or the IFN-γ : IL-10 ratio ( r = −0·89) were also seen. We suggest that the magnitude of the IFN-γ inflammatory response triggered by ML can be driven by the time of leishmanial antigens exposition during the active phase of the disease. This pattern could persist even long-term after cure. However, despite IFN-γ levels, the decrease of the TNF and IFN-γ : IL-10 ratio reflects the control of proinflammatory responses achieved by cure of ML, possibly preventing disease relapses. [ABSTRACT FROM AUTHOR]