title: 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.
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.
authors.affiliation: Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.affiliation: Division of Biotechnology, Netaji Subhas Institute of Technology, New Delhi 110078, India; Department of Biochemistry, Banaras Hindu University, India. Electronic address: rajiv082@yahoo.com.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Immunology & Infection Lab, QIMR Berghofer Medical Research Institute, Herston, 4006, Australia.
authors.forename: Christian
authors.initials: C
authors.lastname: Engwerda
authors.affiliation: National Institute of Allergy & Infectious Disease, National Institute of Health, Bethesda, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sacks
authors.affiliation: Department of Microbiology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nylen
authors.affiliation: Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. Electronic address: drshyamsundar@hotmail.com.
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D007893:Leishmania donovani / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D010271:Parasites / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Enbrel; IL-10; Splenic aspirate; TNF-α; Visceral leishmaniasis; Whole blood assay