TY - JOUR
T1 - Role of IL-1β IL-6 and TNF-α cytokines and TNF-α promoter variability in Plasmodium vivax infection during pregnancy in endemic population of Jharkhand, India
AU - Singh, Krishn Pratap
AU - Shakeel, Shayan
AU - Naskar, Namrata
AU - Bharti, Aakanksha
AU - Kaul, Asha
AU - Anwar, Shadab
AU - Kumari, Shweta
AU - Kumar, Amod
AU - Singh, Jiv Kant
AU - Kumari, Nutan
AU - Gupta, Birendra Kumar
AU - Manna, Purwa
AU - Roy, Vishwaprakash
AU - Lata, Sneh
AU - Singh, Om P.
AU - Sinha, Manoranjan Prasad
AU - Sharma, Ajay Kumar
AU - Sohail, Mohammad
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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-1β TNF-α and IL-6) employing ELISA in a stratified group of samples and the plausible genetic association of TNF-α −308 G/A using PCR-RFLP/sequencing during Plasmodium vivax infection in pregnancy. Results: We observed significantly elevated concentrations of IL-1β were observed, followed by IL-6 and TNF-α in women with malaria (WWM) and in malaria in pregnancy (MIP). Further, elevated IL-1β followed by TNF-α 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-1β in healthy pregnancies. In the second trimester, however, we observed a high level of IL-1β in the MIP group compared to a sustained high level of IL-1β in the healthy pregnancy group. In the third trimester, high IL-1β was sustained in the MIP group and healthy pregnancies acquired a high TNF-α level. The genotypic distribution for the TNF-α 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-α 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-1β and IL-6 in MIP and TNF-α in WWM may be regarded as a prognostic inflammatory marker of infection and pregnancy. Most particularly, the TNF-α 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.
AB - 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-1β TNF-α and IL-6) employing ELISA in a stratified group of samples and the plausible genetic association of TNF-α −308 G/A using PCR-RFLP/sequencing during Plasmodium vivax infection in pregnancy. Results: We observed significantly elevated concentrations of IL-1β were observed, followed by IL-6 and TNF-α in women with malaria (WWM) and in malaria in pregnancy (MIP). Further, elevated IL-1β followed by TNF-α 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-1β in healthy pregnancies. In the second trimester, however, we observed a high level of IL-1β in the MIP group compared to a sustained high level of IL-1β in the healthy pregnancy group. In the third trimester, high IL-1β was sustained in the MIP group and healthy pregnancies acquired a high TNF-α level. The genotypic distribution for the TNF-α 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-α 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-1β and IL-6 in MIP and TNF-α in WWM may be regarded as a prognostic inflammatory marker of infection and pregnancy. Most particularly, the TNF-α 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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U2 - 10.1016/j.molimm.2018.03.019
DO - 10.1016/j.molimm.2018.03.019
M3 - Article
AN - SCOPUS:85044474670
SN - 0161-5890
VL - 97
SP - 82
EP - 93
JO - Molecular Immunology
JF - Molecular Immunology
ER -
