Interleukin-10 inhibits tumor necrosis factor production but not antigen-specific lymphoproliferation in acute Plasmodium falciparum malaria.
In vivo interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma production was measured at the mRNA transcript and protein levels in patients acutely infected with Plasmodium falciparum and during convalescence. Both IL-10 and IFN-gamma but not IL-2 were produced regardless of the patients' clinical severity. IL-4 production was variable. Circulating IFN-gamma and IL-10 were significantly higher in patients with severe disease (P < .01 and .001, respectively). In vitro stimulation of peripheral blood mononuclear cells (PBMC) by malarial antigens during acute infection showed that although there was no lymphoproliferation, the cells could produce IL-10 and IFN-gamma. Recombinant human IL-10 completely abolished in vitro tumor necrosis factor (TNF)-alpha production in response to malarial antigens, as well as the antigen-specific proliferative response of convalescent patients. However, anti-IL-10 was insufficient to restore proliferation of PBMC from acutely infected patients. These findings suggest that IL-10 may have an important negative feedback action on the production of inflammatory cytokines in acute falciparum malaria without contributing to the defect in antigen-specific proliferation.
Ho
M
M
Department of Microbiology and Infectious Diseases, University of Calgary, Canada.
Sexton
M M
MM
Tongtawe
P
P
Looareesuwan
S
S
Suntharasamai
P
P
Webster
H K
HK
D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000494:pharmacology; D002478:Cells, Cultured; D003289:Convalescence; D015342:DNA Probes; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D010963:Plasmodium falciparum / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000953:Antigens, Protozoan; D015342:DNA Probes; D007376:Interleukin-2; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma