Adjunct Therapy of rIFN-γ and rIL-17A along with Suboptimal Dose of Amphotericin-B effectively Control the Leishmania donovani Parasitic Growth in Infected Mice

Abstract

Containment/dissemination of Leishmaniasis depends on the dominance of Th1/ Th2 immunity. IFN-γ and IL-17A are well known for protection from leishmaniasis. Synergistic effects of these two cytokines are also known in various autoimmune diseases. However, the therapeutic, as well as adjunct therapeutic use of rIL-17A and rIFN-γ in combination with sub-optimal dose of amphotericin-B (AmpB) is still not validated in visceral leishmaniasis. In the present study, we have evaluated the adjunct therapy in a mouse model of VL. After twenty-one days of post infection, in the therapeutic group, mice were intra-peritoneally injected with two doses of recombinant cytokines at one week interval. In adjunct therapeutic groups of mice, immune components were primed for three days with recombinant cytokine(s) followed by injection of sub-optimal dose of AmpB. Body weight, parasitic load in visceral organs and fold change in cytokines’ gene expression was evaluated. We observed significant gain in body weight, inhibition of parasitic load in visceral organs {(liver; 71.7% - 95%), (spleen; 70%-88.7%) (Bone marrow; 46.6 -87.1%)}; significant up regulation in fold change of proinflammatory cytokine(s) gene expression (TNF-γ,iNOS, IL-2 and IL-12) as well as marginal increase of anti-inflammatory cytokine(s) gene expression (IL-4, IL-10&TGF-γ} in adjunct therapeutic groups of mice. Our results suggest that though the therapeutic use of recombinant cytokine(s) is not the best option; however, use of recombinant cytokine(s) along with suboptimal dose of amphoterocin-B to reduce drug toxicity could have a way for better treatment options.

Keywords

• balb/c mice
• il-17
• therapeutic
• adjunct therapy
• visceral leishmaniasis