Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-γ production by spleen cells from human visceral leishmaniasis patients

The pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha has an important role in control of experimental Leishmania donovani infection. Less is known about the role of TNF-alpha in human visceral leishmaniasis (VL). Evidence for a protective role is primarily based on case reports of VL development in individuals treated with TNF-alpha neutralizing antibody. In this study, we have evaluated how TNF-alpha neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (SA) from active VL patients. The effect of TNF-alpha neutralization on cell mediated antigen specific responses were also evaluated using whole blood cultures. Neutralization of TNF-alpha did not affect parasite numbers in SA cultures. Interferon (IFN)-gamma levels were significantly reduced, but interleukin (IL)-10 levels were unchanged in these cultures. Leishmania antigen stimulated SA produced significant TNF-alpha which suggests that TNF-alpha is actively produced in VL spleen. Further it stimulates IFN-gamma production, but no direct effect on parasite replication. (C) 2016 Elsevier Ltd. All rights reserved.