Plasma levels of TNF-alpha soluble receptors correlate with outcome in human falciparum malaria.

Plasma from immune (residents of malaria infested areas) and non immune (European travellers) patients suffering from cerebral malaria, severe or mild, was analyzed for the presence of soluble tumor necrosis factor receptors. On admission of the subjects, sTNF-R55 and sTNF-R75 levels were significantly elevated in all groups and correlated with TNF-alpha. Except for sTNF-R55 whose levels were higher in severe than in mild malaria, no correlation was observed between soluble receptors and clinical status. Nevertheless, sTNF-R55 and sTNF-R75 were significantly more elevated in patients who died (10.7 +/- 2.3 ng/ml and 94.9 +/- 31 ng/ml, respectively) than in those surviving (5.5 +/- 0.4 ng/ml and 37.4 +/- 5.4 ng/ml respectively). A marked correlation was observed between soluble receptors levels and some biological markers of gravity like creatinine, urea, and bilirubin. In 13 non immune patients, circulating soluble receptors levels decreased significantly after 7 days when clinical and biological malaria features had disappeared, but TNFsR75 remained above normal levels. After a fortnight of treatment in 17 immune patients, sTNF-R55 and sTNF-R75 remained elevated. However, the ratios of TNF-alpha/s TNF-R55 and 75 were not higher in the cases of cerebral malaria or fatal outcome. Further studies are required to determine if elevated levels of sTNF-R55 and sTNF-R75 are beneficial, due to the inhibition of TNF-alpha or whether they are detrimental since they stabilize this deleterious cytokine.