Singh, Krishn Pratap; Shakeel, Shayan; Naskar, Namrata; Bharti, Aakanksha; Kaul, Asha; Anwar, Shadab; Kumari, Shweta; Kumar, Amod; Singh, Jiv Kant; Kumari, Nutan; Gupta, Birendra Kumar; Manna, Purwa; Roy, Vishwaprakash; Lata, Sneh; Singh, Om P; Sinha, Manoranjan Prasad; Sharma, Ajay Kumar; Sohail, Mohammad
Role of IL-1 beta, IL-6 and TNF-alpha cytokines and TNF-alpha promoter variability in Plasmodium vivax infection during pregnancy in endemic population of Jharkhand, India
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  • Molecular immunology, 2018-05-01, Vol.97, p.82-93
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Background: The combinatorial effects of Plasmodium infection, perturbation of inflammatory responses and the dichotomic role of TNF promoter polymorphism has potential clinical and physiological relevance during pregnancy. Objective and Methods: This coordinated orchestration instigated us to investigate the circulating level of inflammatory cytokines (IL-1 beta, TNF-alpha and IL-6) employing ELISA in a stratified group of samples and the plausible genetic association of TNF-alpha - 308 G/A using PCR-RFLP/sequencing during Plasmodium vivax infection in pregnancy. Results: We observed significantly elevated concentrations of IL-1 beta were observed, followed by IL-6 and TNF-alpha in women with malaria (WWM) and in malaria in pregnancy (MIP). Further, elevated IL-beta, followed by TNF-alpha and IL-6 were detected in the non-infected pregnancy group. The differential dynamics of inflammatory cytokine concentration during each trimester of pregnancy with and without P. vivax infection were detected. For the first time, a high level of IL-6 was observed in the first trimester of MIP and high IL-beta in healthy pregnancies. In the second trimester, however, we observed a high level of IL-1 beta in the MIP group compared to a sustained high level of IL-1 beta in the healthy pregnancy group. In the third trimester, high was sustained in the MIP group and healthy pregnancies acquired a high TNF-alpha level. The genotypic distribution for the TNF-alpha promoter - 308 G/A position was observed to be nonsignificant and mildly associated during MIP (OR = 1.4) and in WWM (OR = 1.2). Moreover, based on genotypic distribution, we observed a well-correlated and significantly elevated TNF-alpha concentration in the mutant homozygote genotype (AA; p = 0.001) followed by heterozygotes (GA; p = 0.0001) and ancestral genotypes (GG; p = 0.0001) in both MIP and WWM subjects. Conclusion: The observation of elevated IL-1 beta and IL-6 in MIP and TNF-a in WWM may be regarded as a prognostic inflammatory marker of infection and pregnancy. Most particularly, the TNF-alpha concentration and its polymorphic variability in the promoter region may indicate genetic susceptibility and mildly influence the risk for P. vivax infection during pregnancy and in women with malaria.

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