Prediction of Accelerated Cure in Plasmodium falciparum Malaria by the Elevated Capacity of Tumor Necrosis Factor Production

Peter G. KremsnerInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Stefan WinklerInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Christian BrandtsInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Eckart WildlingInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Lars JenneInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Wolfgang GraningerInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Javier PradaInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Ulrich BienzleInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Pierre JuillardInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Georges E. GrauInternational Research Laboratory, Albert-Schweitzer-Hospital, Institut fur Tropenmedizin, Department of Infectious Diseases, University of Vienna, Department of Pathology, University of Geneva, Lamabarene, Gabon

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Cytokine regulation was compared in three groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy: adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria. Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, TNF receptors (TNF R), and the TNF/TNF R ratios were significantly higher in severe malaria compared with uncomplicated malaria. High plasma levels of all immunoregulatory molecules were associated with slow cure after therapy. In all patients, phytohemagglutinin-induced cytokine production was depressed on admission compared with convalescence. A significant difference was the higher TNF production capacity in patients with severe malaria on day 2 and day 5 compared with that in patients with uncomplicated malaria. In contrast to IL-6 and IL-8, a high TNF production capacity during the acute phase of malaria predicted a rapid clinical and parasitologic cure in the patients. These findings illustrate the dual role of TNF in the protection and pathology of malaria.

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