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Infection and Immunity, September 1999, p. 4977-4981, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Blood Mononuclear Cell Nitric Oxide Production and Plasma Cytokine Levels in Healthy Gabonese Children with Prior Mild or Severe Malaria

Douglas J. Perkins,1,2 Peter G. Kremsner,2,3 Daniela Schmid,2,3 Mary A. Misukonis,1 Meghan A. Kelly,1 and J. Brice Weinberg1,*

Department of Medicine, VA and Duke University Medical Centers, Durham, North Carolina1; Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon2; and Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany3

Received 31 March 1999/Returned for modification 11 May 1999/Accepted 9 June 1999

Plasmodium falciparum malaria is an important cause of morbidity and mortality in children. Factors that determine the development of mild versus severe malaria are not fully understood. Since host-derived nitric oxide (NO) has antiplasmodial properties, we measured NO production and NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMC) from healthy Gabonese children with a history of prior mild malaria (PMM) or prior severe malaria (PSM) caused by P. falciparum. The PMM group had significantly higher levels of NOS activity in freshly isolated PBMC and higher NO production and NOS activity in cultured PBMC. The investigation of NO-modulating cytokines (e.g., interleukin 12, gamma interferon, tumor necrosis factor alpha [TNF-alpha ], and transforming growth factor beta 1) as an explanation for differing levels of NOS activity revealed that plasma levels of TNF-alpha were significantly higher in the PSM group. Our results suggest that NOS/ NO and TNF-alpha are markers for prior disease severity and important determinants of resistance to malaria.

* Corresponding author. Mailing address: VA and Duke University Medical Centers, 508 Fulton St., Durham, NC 27705. Phone: (919) 286-6833. Fax: (919) 286-6891. E-mail: brice{at}acpub.duke.edu.

Infection and Immunity, September 1999, p. 4977-4981, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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