PLASMA-LEVELS OF TNF-ALPHA SOLUBLE RECEPTORS CORRELATE WITH OUTCOME IN HUMAN FALCIPARUM-MALARIA

Plasma from immune (residents of malaria infested areas) and non immun e (European travellers) patients suffering from cerebral malaria, seve re or mild, was analyzed for the presence of soluble tumor necrosis fa ctor receptors. On admission of the subjects, sTNF-R55 and sTNF-R75 le vels were significantly elevated in all groups end 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 a nd clinical status. Nevertheless, sTNF-R55 and sTNF-R75 were significa ntly 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 observe d between soluble receptors levels and some biological markers of grav ity like creatinine, urea, and bilirubin. In 13 non immune patients, c irculating soluble receptors levels decreased significantly after 7 da ys when clinical and biological malaria features had disappeared, but TNFsR75 remained above normal levels. After a fortnight of treatment i n 17 immune patients, sTNF-R55 and sTNF-R75 remained elevated. However , the ratios of TNF-alpha/sTNF-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 benefical, due to the inhibition of TNF-alpha or whether they are detrimental sin ce they stabilize this deleterious cytokine.