title: Can interferon-gamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection?
abstract: Suitable levels of interferon (IFN)-gamma and interleukin (IL)-10 seem to favour the outcome of cutaneous leishmaniasis (CL), while high IFN-gamma 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-gamma 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-gamma 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-gamma/IL-10 ratio observed in CML can indicate unfavourable cytokine balance. On the other hand, no significant difference in the IFN-gamma/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-gamma/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-gamma/IL-10 balance observed in CCL, SH and ASY individuals can represent a better-modulated immune response associated with a favourable prognosis.
authors.affiliation: Laboratório de Imunoparasitologia, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Gomes-Silva
authors.forename: R
authors.initials: R
authors.lastname: de Cássia Bittar
authors.forename: R
authors.initials: R
authors.lastname: Dos Santos Nogueira
authors.forename: V S
authors.initials: VS
authors.lastname: Amato
authors.forename: M
authors.initials: M
authors.lastname: da Silva Mattos
authors.forename: M P
authors.initials: MP
authors.lastname: Oliveira-Neto
authors.forename: S G
authors.initials: SG
authors.lastname: Coutinho
authors.forename: A M
authors.initials: AM
authors.lastname: Da-Cruz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy / Q000276:immunology*; D007897:Leishmaniasis, Mucocutaneous / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000953:Antigens, Protozoan; D000981:Antiprotozoal Agents; D016753:Interleukin-10; D007371:Interferon-gamma