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. (September 2016)

• Record Type: Journal Article
• Authors: Singh, Neetu; Kumar, Rajiv; Engwerda, Christian; Sacks, David; Nylen, Susanne; Sundar, Shyam
• Is Part Of: Cytokine. Volume 85(2016)
• Page Start: 184
• Page End: 190
• Publication Date: 2016-09
• Subjects: VL visceral leishmaniasis -- SA splenic aspirate -- TB tuberculosis -- SLA soluble leishmania antigen -- PHA phytohemagglutinin -- TNF-α tumor necrosis factor-α -- IFN-γ interferon-γ -- IL-10 interleukin-10 -- TNF-RI tumor necrosis factor receptor type I -- TNF-RII tumor necrosis factor receptor type II -- NO nitric oxide; Visceral leishmaniasis -- TNF-α -- Enbrel -- IL-10 -- Splenic aspirate -- Whole blood assay; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.06.013
• Languages: English
• ISSNs: 1043-4666

Abstract

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