title: Relationship between antipyretic effects and cytokine levels in uncomplicated falciparum malaria during different treatment regimes.
abstract: 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.
authors.affiliation: Malaria Research Unit (M9), Division of Infectious Diseases, Department of Medicine, Karolinska University Hospital, 17176 Stockholm, Sweden. ehugosson@hotmail.com
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hugosson
authors.forename: Scott M
authors.initials: SM
authors.lastname: Montgomery
authors.forename: Zul
authors.initials: Z
authors.lastname: Premji
authors.forename: Marita
authors.initials: M
authors.lastname: Troye-Blomberg
authors.forename: Anders
authors.initials: A
authors.lastname: Björkman
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005334:Fever / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000276:immunology*; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011739:Pyrimethamine / Q000008:administration & dosage; D018709:Statistics, Nonparametric; D013413:Sulfadoxine / Q000008:administration & dosage; D013636:Tanzania
chemical_list: D018712:Analgesics, Non-Narcotic; D000962:Antimalarials; D016207:Cytokines; D004338:Drug Combinations; D000082:Acetaminophen; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine