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

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.