Krishn Pratap Singh1, Shayan Shakeel2, Namrata Naskar3, Aakanksha Bharti4, Asha Kaul5, Shadab Anwar6, Shweta Kumari2, Amod Kumar2, Jiv Kant Singh7, Nutan Kumari8, Birendra Kumar Gupta2, Purwa Manna9, Vishwaprakash Roy9, Sneh Lata10, Om P Singh5, Manoranjan Prasad Sinha11, Ajay Kumar Sharma12, Mohammad Sohail13. 1. Research Laboratory, University Department of Zoology, Vinoba Bhave University, Hazaribag, Jharkhand, India; Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Patna, India. 2. Research Laboratory, University Department of Zoology, Vinoba Bhave University, Hazaribag, Jharkhand, India. 3. Female OPD, Kasturba Medical College, Karnataka, India. 4. Research Laboratory, University Department of Zoology, Vinoba Bhave University, Hazaribag, Jharkhand, India; Department of Biotechnology, VIT University, Vellore, India. 5. Division of Parasitology, National Institute of Malaria Research, New Delhi, India. 6. Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Patna, India. 7. Department of Biotechnology, T. N. B. College, Bhagalpur, India. 8. Department of Biochemistry, Patna Medical College and Hospital, Patna, India. 9. Faculty of Life Science, MATS University, Raipur, Chhattisgarh, India. 10. Female OPD, Sadar Hospital, Hazaribag, Jharkhand, India. 11. University Departments of Zoology, Ranchi University, Ranchi, Jharkhand, India. 12. Research Laboratory, University Department of Zoology, Vinoba Bhave University, Hazaribag, Jharkhand, India. Electronic address: ajaysharma@vbu.ac.in. 13. Research Laboratory, University Department of Zoology, Vinoba Bhave University, Hazaribag, Jharkhand, India. Electronic address: soh.khan@vbu.ac.in.
Abstract
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.
BACKGROUND: The combinatorial effects of Plasmodiuminfection, 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 vivaxinfection 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. vivaxinfection 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. vivaxinfection during pregnancy and in women with malaria.