Can interferon-γ and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection?

Abstract

Summary Suitable levels of interferon (IFN)-γ and interleukin (IL)-10 seem to favour the outcome of cutaneous leishmaniasis (CL), while high IFN-γ and low IL-10 production are associated with severity of mucosal leishmaniasis (ML). Considering that cytokine balance is important for the maintenance of protective responses in leishmaniasis, our aim was to investigate leishmanial antigens-induced IFN-γ and IL-10 levels maintained in healed individuals who had different clinical outcomes of Leishmania infection. Thirty-three individuals who recovered from L. braziliensis infection were studied: cured CL (CCL), cured ML (CML), spontaneous healing of CL (SH) or asymptomatic individuals (ASY). Cytokines were quantified by enzyme-linked immunosorbent assay (ELISA) in culture supernatants of L. braziliensis-stimulated peripheral blood mononuclear cells (PBMC). IFN-γ levels were higher in CML (7593 ±  5994 pg/ml) in comparison to SH (3163 ± 1526 pg/ml), ASY (1313 ±  1048 pg/ml) or CCL (1897 ± 2087 pg/ml). Moreover, cured ML cases maintained significantly lower production of IL-10 (127 ± 57·8 pg/ml) in comparison to SH (1373 ± 244 pg/ml), ASY (734 ± 233 pg/ml) or CCL (542 ±  375 pg/ml). Thus, a high IFN-γ/IL-10 ratio observed in CML can indicate unfavourable cytokine balance. On the other hand, no significant difference in the IFN-γ/IL-10 ratio was observed when CCL individuals were compared to SH or ASY subjects. In conclusion, even after clinical healing, ML patients maintained a high IFN-γ/IL-10 secretion profile in response to leishmanial antigens. This finding can explain a delayed down-modulation of exacerbated inflammatory responses, which can be related in turn to the necessity of prolonged therapy in ML management. Conversely, lower IFN-γ/IL-10 balance observed in CCL, SH and ASY individuals can represent a better-modulated immune response associated with a favourable prognosis.