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

Abstract

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 cytometrybased 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.

HIV, Cytomegalovirus, and Malaria Infections during Pregnancy Lead to Inflammation and Shifts in Memory B Cell Subsets in Kenyan Neonates

“…Cord blood IP-10 levels of Kenyan neonates in our study were similar to the lower placental IP-10 levels of Malawian HIV infected non-transmitter pairs (cord blood cytokines were not measured in this study). Multiple studies have shown that Pf infection in pregnancy is associated with adverse outcomes and elevated pro-inflammatory cytokines/chemokines (71–75). Few, however, have shown differences between maternal plasma levels at delivery and cord blood levels.…”

Evaluation of Interleukin 2, Interleukin 10, and Interferon Gamma Among Pregnant Women Co-infected With HIV and Plasmodium falciparum

“…Malaria and HIV are 2 of the most common and important health problems in sub-Saharan African countries, and pregnant women are particularly a vulnerable group (21). In pregnancy, the body undergoes modulation of pro-inflammation responses to ensure fetal survival (22). These adjustments may decrease maternal immune defenses and promote infections (17).…”

“…These adjustments may decrease maternal immune defenses and promote infections (17). HIV infection may impair immunity to malaria by altering cytokine profile Effect of malaria on the CD4 count and the tested cytokines among pregnant women (22). A number of factors have been reported to influence cytokine levels in an individual (23).…”

Evaluation of Serum Interleukin 6, Tumor Necrosis Factor-Alpha, and Interferon-Gamma Levels in Relation to Body Mass Index and Blood Pressure in HIV Seropositive Pregnant Women Coinfected with Malaria

“…A positive correlation between IL-6 and TNF-α was also observed in HIV seropositive pregnant women with malaria coinfection. Further studies have indicated that acute malaria can also increase cytokine production which could subsequently lead to viral replication and immunological interactions [9,25]. In HIV infection, molecular redox balance is disturbed in CD4 + T cells which are accompanied by severe immune dysfunction thus, potentiating HIV replication.…”

“…is can easily occur due to reduced immunity [5] which also enhances coinfections such as malaria especially in places of high endemic transmission [6]. Reports have shown evidence of increased risk of placental malaria in HIV-infected pregnant women [7], which can grossly reduce their immunity to malaria infection leading to modulation of circulating cytokines [8] with synergistic exposure to adverse pregnancy outcomes [9].…”