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ELEVATED PLASMA LEVELS OF INTERFERON (IFN)-, IFN- INDUCING CYTOKINES, AND IFN- INDUCIBLE CXC CHEMOKINES IN VISCERAL LEISHMANIASIS

Interferon (IFN)- plays an important role during immune responses against leishmaniasis. Production of IFN- is regulated by interleukin (IL)-12, IL-18, and IL-15. Interferon--inducible protein (IP)-10 and monokine induced by IFN- (Mig) are CXC chemokines, the production of which, at least in part, is IFN- dependent. A follow-up study of individuals infected with Leishmania donovani was undertaken in an area of Ethiopia endemic for visceral leishmaniasis (VL). Plasma levels of IFN-, IL-12p40, IL-18, IL-15, IP-10, and Mig were markedly elevated in symptomatic VL patients (n = 70) compared with individuals with asymptomatic Leishmania infections (n = 39), malaria patients (n = 13), and healthy controls from the endemic area (n = 12). A significant decrease of IFN- and all mediators was observed after treatment of VL patients (n = 33). These data show that increased plasma levels of IFN-, as well as the mediators involved in the production and the activity of this cytokine, are characteristic of active VL in humans, and may play an important immunopathogenic role. The data also suggest that in patients with VL, the production of type 1 cytokines is not depressed, but there appears to be an unresponsiveness to the stimuli of type 1 cytokines. The underlying causes of immunologic unresponsiveness remain a subject of further investigation.

Received January 22, 2004. Accepted for publication June 9, 2004.

Acknowledgments: We thank the staff of the Karat Health Centre in Konso for the carefully and diligently rendered patient care. The field study was undertaken in the Konso District in southwestern Ethiopia. Pentostam (sodium antimony gluconate; The Wellcome Foundation Ltd., London, United Kingdom) was provided by Médecins sans Frontières of The Netherlands. We also thank the technical staff of the Institute of Pathobiology of Addis Ababa University for clinical laboratory work and collecting blood samples.

Financial support: Asrat Hailu was supported by the Netherlands Foundation for the Advancement of Tropical Research (WOTRO). This study was supported by WOTRO, the Research and Publications Office, Addis Ababa University; and L’Agence pour l’Investis-sement dans la Recherche a l’Etranger Développement of the French Government.

Authors’ addresses: Asrat Hailu, Faculty of Medicine, Department of Microbiology, Immunology and Parasitology, and Institute of Pathobiology, Addis Ababa University, PO Box 9086, Addis Ababa, Ethiopia and Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center; University of Amsterdam, Amsterdam, The Netherlands, Telephone: 251-1-533-197, Fax: 251-1-513-099, E-mails: a_hailu{at}hotmail.com and hailu_a2004{at}yahoo.com. Tom van der Poll, Department of Internal Medicine, Laboratory of Experimental Internal Medicine, and Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS; Academic Medical Center; University of Amsterdam; Amsterdam, the Netherlands. Nega Berhe, Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia. Piet A. Kager, Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center; University of Amsterdam, Amsterdam, The Netherlands.

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