Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severe P. falciparum malaria patients in Sri Lanka

Abstract

Plasma levels of pro- and anti-inflammatory cytokines of Plasmodium falciparum-infected patients with severe malaria (SM; n = 62) and uncomplicated malaria (UM; n = 69) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-alpha (P<0·01), IL-6 (P<0·01), and IL-10 (P<0·05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-alpha levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n = 14) were significantly higher than those of the UM patients (P<0·001) and comparable to SM patients. Plasma IFN-gamma levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group, whereas percentages of parasitemia in all three groups were comparable. Analysis of plasma TNF-alpha levels and the ratio of TNF-alpha/IL-10 in UM (n = 34) and SM (n = 34) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNF-alpha levels as well as TNF-alpha/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P<0·05). These results suggest that the high circulating TNF-alpha levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.

Keywords:

• P. falciparum
• Tumor necrosis factor-alpha
• Interleukin-10
• Severe malaria
• Sri Lanka

Acknowledgements

We gratefully acknowledge the cooperation of the staff of the National Hospital of the Sri Lanka and the General Hospital of Anuradhapura. We wish to thank S. Bandara, K. L. R. L. Perera, G. M. Kapilananda, N. Fernando, S. D. Abeynayeka, K. Ekanayaka, C. Wimalasena, J. Rajakaruna, and Priyankara Perera for technical assistance. This investigation received support from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Disease (TDR), grant ID 930807, ID 94304, and ID 960603.