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Randomized Controlled Trial
. 2015 Aug;93(2):287-92.
doi: 10.4269/ajtmh.14-0653. Epub 2015 Jun 22.

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

Samad A Ibitokou  1 , Lise Denoeud-Ndam  1 , Sèm Ezinmegnon  1 , Rodolphe Ladékpo  1 , Djimon-Marcel Zannou  1 , Achille Massougbodji  1 , Pierre-Marie Girard  1 , Michel Cot  1 , Adrian J F Luty  1 , Nicaise Tuikue Ndam  2
Affiliations
Randomized Controlled Trial

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

Samad A Ibitokou et al. Am J Trop Med Hyg. 2015 Aug.

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.

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Conflict of interest statement

Disclosure: The funding sources had no involvement in the design, collection, analysis, and interpretation of data, writing of the manuscript or decision to publish.

Figures

Figure 1.
Figure 1.
Human immunodeficiency virus (HIV) infection-related changes in plasma cytokines levels between inclusion and delivery in 200 pregnant women included in our study. Scatter plots include bars depicting medians of Th1 (IL-2, TNF-α, IFN-γ) and Th2 (IL-4, IL-5, IL-10) cytokines measured in plasma samples. Cytokine levels are represented in log10 on the left (y) axis. Numbers of women with detectable levels of cytokines are as follows, at Inclusion: IL-2 (n = 23), IL-4 (n = 47), IL-5 (n = 54), IL-10 (n = 62), TNF-α (n = 63), IFN-γ (n = 65, and at delivery: IL-2 (n = 25), IL-4 (n = 41), IL-5 (n = 68), IL-10 (n = 95), TNF-α (n = 30), IFN-γ (n = 44). The statistical significance of differences between inclusion and delivery were determined using the Wilcoxon paired test (* P < 0.05, ** P < 0.01, *** P < 0.001).
Figure 2.
Figure 2.
IL-5 and IL-10 levels in pregnant women with low and high CD4 T cell counts at inclusion. Scatter plots include bars depicting medians with interquartile ranges of IL-5 and IL-10 measured in 98 pregnant women with CD4+ T cell count > 350/mm3 compared to 102 women with CD4+ T cell count < 350/mm3. Cytokine levels are represented in log10 on the left (y) axis. The non-parametric Mann Whitney U test was used to determine the significance of differences in cytokine levels.
Figure 3.
Figure 3.
IL-5 level at inclusion and delivery in pregnant women with and without ART at Inclusion. Scatter plots include bars depicting medians with interquartile ranges of IL-5 measured at Inclusion (A) and at delivery (B) in 117 pregnant women without ART compared to 83 under ART at inclusion. IL-5 concentration was presented as the absolute level of cytokine on the left (y) axis. The non-parametric Mann Whitney U test was used to determine the significance of differences in cytokine levels (* P < 0.05).
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