Insights Into Circulating Cytokine Dynamics During Pregnancy in HIV-Infected Beninese Exposed to Plasmodium falciparum Malaria

Am J Trop Med Hyg. 2015 Aug;93(2):287-92. doi: 10.4269/ajtmh.14-0653. Epub 2015 Jun 22.

Abstract

We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array. Significantly elevated levels of IL-10 and lower levels of TNF-α were observed at delivery compared with inclusion (P = 0.005). At inclusion, the presence of circulating IFN-γ, a higher CD4(+) T cell count and having initiated intermittent preventive treatment of malaria with sulfadoxine pyrimethamine (SP-IPTp) were all associated with a lower likelihood of Plasmodium falciparum infection. At delivery, the inverse relationship between the presence of infection and circulating IFN-γ persisted, although there was a positive association between the likelihood of infection and the presence of circulating TNF-α. Initiation of antiretroviral therapy was associated with elevated IL-5 production. Consistent with our own and others' observations in HIV seronegative subjects, this study shows circulating IL-10 to be a marker of infection with P. falciparum during pregnancy even in HIV-infected women, although plasma IFN-γ may be a marker of anti-malarial protection in such women.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimalarials / therapeutic use
  • Benin / epidemiology
  • Drug Combinations
  • Female
  • HIV Infections / blood*
  • HIV Infections / complications
  • Humans
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Interleukin-4 / blood
  • Interleukin-5 / blood
  • Malaria, Falciparum / blood*
  • Malaria, Falciparum / complications
  • Malaria, Falciparum / drug therapy
  • Pregnancy
  • Pregnancy Complications, Infectious / blood*
  • Pregnancy Complications, Infectious / virology*
  • Pregnancy Complications, Parasitic / blood*
  • Pregnancy Complications, Parasitic / drug therapy
  • Prospective Studies
  • Pyrimethamine / therapeutic use
  • Sulfadoxine / therapeutic use
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult

Substances

  • Antimalarials
  • Drug Combinations
  • Interleukin-2
  • Interleukin-5
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • fanasil, pyrimethamine drug combination
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Sulfadoxine
  • Pyrimethamine