Relationship between antipyretic effects and cytokine levels in uncomplicated falciparum malaria during different treatment regimes.

We have previously shown that both chloroquine and paracetamol (acetaminophen) have antipyretic activity during treatment of acute uncomplicated Plasmodium falciparum malaria in children 1-4 years old. Here, we studied if this effect was accompanied by changes in plasma cytokine levels. The 104 children were treated with either chloroquine or sulfadoxine/pyrimethamine (SP) alone, SP+chloroquine or SP+paracetamol for 4 days. Cytokine levels were determined days 0, 2 and 3, body temperature every sixth hour until 72h and parasitemia once daily for 4 days. At admission, body temperature correlated with levels of IL-10, IFN-gamma and IL-6, and parasitemia correlated with IL-10 and IL-6. Except for TNF-alpha and IL-1beta, where no significant effect was found, all cytokine levels (IL-10, IFN-gamma, IL-6, IL-12, IL-13, IL-18 and IL-4) decreased up to day 2 (p<0.05). IL-6 levels continued to fall from days 2 to 3 (p<0.05), whereas increased levels were found for several cytokines (IL-12, IL-13, IL-18 and IL-1beta) (p<0.05). The antipyretic effects of chloroquine and paracetamol could not be related to any specific changes in the evaluated cytokine production or in Th1/Th2 or inflammatory/anti-inflammatory cytokine ratios. Alternative mechanisms for antipyretic effects and associations between fever and cytokine levels during uncomplicated P. falciparum malaria are therefore discussed.