Cortisol, Prolactin, Cytokines and susceptibility of Pregnant Sudanese Women to Plasmodium falciparum Malaria

Abstract

Introduction: Globally, 200 million pregnant women infected with malaria each year. Pregnant women are more susceptible to malaria infection than nonpregnant ones. It has been proposed that nonspecific immunosuppression may be caused by pregnancyassociated hormones. Cortisol and prolactin are among the most important candidates which affect maternal immunity to Plasmodium falciparum malaria. Understanding the hormonal and cytokine interactions that underlie susceptibility to the disease should be helpful in elucidating the pathogenesis of Plasmodium falciparum malaria during pregnancy. Objectives: The current study was conducted in Wad Medani and New Halfa, areas characterized by unstable malarial transmission in central and eastern Sudan, respectively. Its aims were to investigate the role of and interactions between cortisol, prolactin, interferon-γ (IFN-γ), interleukin-4 (IL-4) and interleukin-10 (IL-10) in pregnant women with Plasmodium falciparum malaria and to investigate the cytokine profiles in peripheral, placental and cord blood in parturient women in these areas. Methods: In Wad Medani, the 82 pregnant subjects who were enrolled either had uncomplicated, Plasmodium falciparum malaria (the 45 cases) or were apparently uninfected and healthy women (the 37 controls) who were well matched to the cases. Five ml of venous blood were withdrawn in plain tube, centrifuged and kept at -20 until processed in the laboratory for cortisol, prolactin and cytokine analysis. Total serum cortisol concentrations were determined with the 125I-F RIA cortisol test kit, whereas125IPRL IRMA prolactin test kit was used to determine serum prolactin concentrations. Enzyme-linked immunosorbent assay was used to measure the concentrations of the three cytokines, IFN-γ, IL-4 and IL-10. In New Halfa, 5 mL of maternal, placental and cord blood was collected immediately after delivery, quickly withdrawn in plain tube and centrifuged and kept at -20 until processed. Enzyme-linked immunosorbent assay was used to measure the concentrations of the three cytokines, IFN-γ, IL-4 and IL-10, in the sera from peripheral, placental and cord blood of 87 parturient women (53 were found to have past placental malaria infections). V Results: Wad Medani, compared with the controls, the cases were found to have significantly higher serum concentrations of total cortisol and IL-10 and significantly lower levels of prolactin and IFN-γ (but similar concentrations of IL-4). The hormone and cytokine concentrations measured in the infected primigravidae were similar to those recorded in the infected multigravidae. Among the cases, there was a significant positive correlation between serum cortisol and IL-10 (r=0.188; P=0.025) and significant negative correlations between prolactin and both IL-4 (r=20.175; P=0.038) and IL-10 (r=20.186; P=0.027) but no significant correlation between prolactin and cortisol. In New Halfa, The concentrations of these cytokines were significantly higher in peripheral and placental sera from uninfected women than in sera from infected women. IFN-γ concentrations were higher in the cord sera from uninfected women in comparison to the infected ones too. The levels of these cytokines were not significantly different between the primigravidae and multigravidae. Cord sera in all the groups had the lower levels of these cytokines. Strong positive correlations were observed between peripheral and placental cytokines. Conclusions: In conclusion, it appears that, irrespective of parity, cortisol, prolactin and certain cytokines are key mediators in the host response to Plasmodium falciparum infection during pregnancy in women living in central Sudan, where malarial transmission is unstable. In eastern Sudan, the patterns of the immune responses that occur in placental, peripheral and cord blood were influenced by the malaria infections, irrespective to the parity. Additionally, immune response during Plasmodium falciparum infection is not different in the peripheral and placental compartments.