Cytokines and dysregulation of the immune response in human malaria.
The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-1 (IL-1) plays on the immunoregulation, and its ability to mimic various features of clinical malaria, reports on IL-1 in malaria are lacking. We found that only 2 out of 35 subjects with acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T-lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72 h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 +/- 2,900) and P. vivax malaria (13,000 +/- 3,300), as compared to that of healthy individuals (27,000 +/- 3,000). Addition of IL-1 partially reversed depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2.
Departamento de Imunologia e Patologia, Universidade Federal de Goiás, Goiânia, Brasil.
M F
MF
Alves
L L
LL
Santos-Neto
M I
MI
Junqueira
C E
CE
Tosta
C E
CE
Costa
D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000097:blood* / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D016780:Malaria, Vivax / Q000097:blood / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; D015232:Dinoprostone; D007213:Indomethacin