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Infection and Immunity, July 2000, p. 3909-3915, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Low Interleukin-12 Activity in Severe Plasmodium falciparum Malariadagger

Adrian J. F. Luty,1,* Douglas J. Perkins,2,Dagger Bertrand Lell,1,3,4 Ruprecht Schmidt-Ott,1,3 Leopold G. Lehman,1,3 Doris Luckner,1,3 Bernhard Greve,1,3 Peter Matousek,3,4 Klaus Herbich,3,4 Daniela Schmid,3 J. Brice Weinberg,2 and Peter G. Kremsner1,3

Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany1; Department of Medicine, VA and Duke University Medical Centers, Durham, North Carolina 270052; Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon3; and Department of Infectious Diseases, Internal Medicine I, University of Vienna, Vienna, Austria4

Received 3 February 2000/Returned for modification 15 March 2000/Accepted 12 April 2000

We compared interleukin-12 (IL-12) and other cytokine activities during and after an acute clinical episode in a matched-pair case-control study of young African children who presented with either mild or severe Plasmodium falciparum malaria. The acute-phase, pretreatment plasma IL-12 and alpha interferon (IFN-alpha ) levels, as well as the acute-phase mitogen-stimulated whole-blood production capacity of IL-12, were significantly lower in children with severe rather than mild malaria. IL-12 levels, in addition, showed strong inverse correlations both with parasitemia and with the numbers of circulating malaria pigment-containing neutrophils. Acute-phase plasma tumor necrosis factor (TNF) and IL-10 levels were significantly higher in those with severe malaria, and the concentrations of both of these cytokines were positively correlated both with parasitemia and with the numbers of pigment-containing phagocytes in the blood. Children with severe anemia had the highest levels of TNF in plasma. In all the children, the levels in plasma and production capacities of all cytokines normalized when they were healthy and parasite free. The results indicate that severe but not mild P. falciparum malaria in young, nonimmune African children is characterized by down-regulated IL-12 activity, contrasting markedly with the up-regulation of both TNF and IL-10 in the same children. A combination of disturbed phagocyte functions resulting from hemozoin consumption, along with reduced IFN-gamma responses, may contribute to these differential effects.

* Corresponding author. Mailing address: Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany. Phone: 49-7071-2980228. Fax: 49-7071-295189. E-mail: adrian.luty{at}uni-tuebingen.de.

dagger This paper is dedicated to the memory of the late Robert N. Mshana.

Dagger Present address: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Chamblee, GA 30341.

Infection and Immunity, July 2000, p. 3909-3915, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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