Interleukin-10 Inhibits Tumor Necrosis Factor Production but Not Antigen-Specific Lymphoproliferation in Acute Plasmodium Falciparum Malaria

J Infect Dis. 1995 Sep;172(3):838-44. doi: 10.1093/infdis/172.3.838.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Animals
  • Antigens, Protozoan / pharmacology
  • Cells, Cultured
  • Convalescence
  • DNA Probes
  • Gene Expression
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / pharmacology*
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Interleukins / biosynthesis*
  • Lymphocyte Activation / drug effects*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / physiopathology
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Antigens, Protozoan
  • DNA Probes
  • Interleukin-2
  • Interleukins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma