Low Interleukin-12 Activity in Severe Plasmodium falciparum Malaria

doi:10.1128/IAI.68.7.3909-3915.2000

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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 Malaria

Adrian J. F. Luty,¹^,^* Douglas J. Perkins,²^, 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-paircase-control study of young African children who presented witheither 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 productioncapacity of IL-12, were significantly lower in children with severerather than mild malaria. IL-12 levels, in addition, showed stronginverse correlations both with parasitemia and with the numbersof circulating malaria pigment-containing neutrophils. Acute-phaseplasma tumor necrosis factor (TNF) and IL-10 levels were significantlyhigher in those with severe malaria, and the concentrations ofboth of these cytokines were positively correlated both with parasitemiaand 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 capacitiesof all cytokines normalized when they were healthy and parasitefree. The results indicate that severe but not mild P. falciparummalaria in young, nonimmune African children is characterizedby down-regulated IL-12 activity, contrasting markedly with theup-regulation of both TNF and IL-10 in the same children. A combinationof disturbed phagocyte functions resulting from hemozoin consumption,along with reduced IFN- $gamma$ responses, may contribute to these differentialeffects.

^* 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.

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

Present address: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control andPrevention, Chamblee, GA30341.

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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