Distribution of TNF-α Among Antenatal Women with Varying Levels of Vitamin D
Keywords:
vitamin D, 25-OH Vitamin D, TNF-α, antenatal, cytokine
Abstract
Background and objective: Vitamin D deficiency in antenatal mothers adversely affects not only the health of pregnant mother but also her child. Vitamin D is crucial for proper immune system functioning and management of cytokine environment. Relationship between vitamin D deficiency and TNF-α may prove useful in early detection of inflammatory conditions in pregnant mothers. Therefore, this study assessed serum vitamin D and TNF-α levels in antenatal mothers. Materials & Methods: 78 serum samples of healthy pregnant mothers were included. Serum 25-OH Vitamin D and TNF-α levels were estimated using commercially available ELISA kits. Results:25-OH Vitamin D levels were inadequate (<32ng/ml) in 94.9% of antenatal cases. Majority (74.4%)had an insufficient (11-32 ng/ml)25-OH Vitamin D level. Mean and median vitamin D levels were 16 ± 7.5 SD and 14.5 ng/ml (3.5-39.5) respectively in antenatal mothers. None or a very weak positive linear relationship was observed between serum 25-OH Vitamin D and TNF-α levels (r: 0.13). No correlation was seen between 25-OH Vitamin D & age and TNF-α & age (r: 0.04; r: 0.06 respectively). Conclusions: In settings where subnormal vitamin D levels are prevalent in antenatal mothers, screening for vitamin D deficiency in early pregnancy with subsequent supplementation if needed is recommended. No correlation was observed between serum vitamin D and pro-inflammatory marker TNF-α levels. Further elaborate studies are required to investigate the effects of vitamin D on cytokine environment especially in pregnant mothers.References
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31. Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, et al. Maternal
vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal
study. Lancet.2006;367:36–43.
32. Farrant HJ, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, Osmond C, Veena SR, Fall CH. Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size. Eur J ClinNutr. 2009 May;63:646-652.
33. Agarwal N, Arya SC. Vitamin D3 Levels in Pregnant Women and Newborns at a Private Tertiary Care Hospital in Delhi, India. Int J Gynecol Obstet. 2011; 113, 240-241.
34. Marwaha RK, Tandon N, Chopra S, Agarwal N, Garg MK, Sharma B, Kanwar RS, Bhadra K, Singh S, Mani K, Puri S. Vitamin D status in pregnant Indian women across trimesters and different seasons and its correlation with neonatal serum 25-hydroxyvitamin D levels. Br J Nutr. 2011;106:1383-1389.
35. Clark DA, Arck PC, Chaouat G. Why did your mother reject you? Immunogenetic determinants of the response to environmental selective pressure expressed at the uterine level. Am J ReprodImmunol. 1999;41:5-22.
36. Raghupathy R. Pregnancy: Success and failure within the Th1/Th2/Th3 paradigm. SeminImmunol. 2001;13:219–227
37. Kupferminc MJ, Peaceman AM, Aderka D, Wallach D, Socol ML. Soluble tumor necrosis factor receptors and interleukin-6 levels in patients with severe preeclampsia. Obstet Gynecol.1996; 88:420-427.
38. Teran E, Escudero C, Moya W, Flores M, Vallance P, Lopez-Jaramillo P. Elevated C-reactive protein and pro-inflammatorycytokines in Andean women with preeclampsia. Int J Gynecol Obstet.2001; 75:243-249.
39. Hill JA, Devoe LD, Bryans CI Jr. Frequency of asymptomatic bacteriuria in preeclampsia. Obstel Gynecol.1986, 67:529-532.
40. Hsu CD, Witter FR. Urogenital infection in preeclampsia. Int J GynecolObstel.1995; 49:271-275.
41. Afshari JT, Ghomian N, Shameli A, Shakeri MT, Fahmidehkar MA, Mahajer E, et al. Determination of Interleukin-6 and Tumor Necrosis Factor-alpha concentrations in Iranian-Khorasanian patients with preeclampsia. BMC Pregnancy Childbirth. 2005 Nov 1;5:14.
42. van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid BiochemMol Biol. 2005;97:93–101.
43. Cantorna MT, Woodward WD, Hayes CE, DeLuca HF. 1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. J Immunol. 1998;160:5314–5319.
44. Zhu Y, Mahon BD, Froicu M, Cantorna MT. Calcium and 1 alpha, 25-dihydroxyvitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease. Eur J Immunol. 2005;35:217–224.
45. Lemire JM. Immunomodulatory role of 1, 25-dihydroxyvitamin D3. J Cell Biochem. 1992;49:26–31.
46. Azizieh F, Alyahya KO, Raghupathy R. Association between levels of vitamin D and inflammatory markers in healthy women. J Inflamm Res. 2016;9:51-57.
2. Sahu M, Bhatia V, Aggarwal A, Rawat V, Saxena P, Pandey A, et al. Vitamin D deficiency in rural girls and pregnant women despite abundant sunshine in northern India. ClinEndocrinol (Oxf). 2009;70:680–684.
3. Dasgupta A, Saikia U, Sarma D. Status of 25(OH)D levels in pregnancy: A study from the North Eastern part of India. Indian J EndocrinolMetab. 2012;16:S405–407.
4. Specker BL. Does vitamin D during pregnancy impact offspring growth and bone? Proc Nutr Soc. 2012;71:38–45.
5. Ota K, Dambaeva S, Han AR, Beaman K, Gilman-Sachs A, Kwak-Kim J. Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Hum Reprod. 2014;29:208–219.
6. Bodnar LM, Klebanoff MA, Gernand AD, Platt RW, Parks WT, Catov JM, et al. Maternal vitamin D status and spontaneous preterm birth by placental histology in the US Collaborative Perinatal Project. Am J Epidemiol. 2014;179:168–176.
7. Hyppönen E, Cavadino A, Williams D, Fraser A, Vereczkey A, Fraser WD, et al. Vitamin D and pre-eclampsia: Original data, systematic review and meta-analysis. Ann NutrMetab. 2013;63:331–340.
8. Lacroix M, Battista MC, Doyon M, Houde G, Ménard J, Ardilouze JL, et al. Lower vitamin D levels at first trimester are associated with higher risk of developing gestational diabetes mellitus. ActaDiabetol. 2014;51:609–616.
9. Bowyer L, Catling-Paull C, Diamond T, Homer C, Davis G, Craig ME. Vitamin D, PTH and calcium levels in pregnant women and their neonates. ClinEndocrinol (Oxf).2009;70:372–377.
10. Mehrotra P, Marwaha RK, Aneja S, Seth A, Singla BM, Ashraf G, et al. Hypovitaminosis D and hypocalcemic seizures in infancy. Indian Pediatr. 2010;47:581–586.
11. Royal College of Obstetricians and Gynaecologists. Vitamin D in Pregnancy. Scientific Impact Paper:43. Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/scientific-impact-papers/vitamin_d_sip43_june14.pdf(accessed 07 September 2018)
12. Yildirim I, Magden K, Hur E. Infection Inflammation and Vitamin D. Clin Microbial. 2013; 2: 116.
13. Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, Gold DR, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J ClinNutr. 2007;85:788–795.
14. Barnes PF, Lu S, Abrams JS, Wang E, Yamamura M, Modlin RL. Cytokine production at the site of disease in human tuberculosis. Infect Immun. 1993
Aug;61:3482-3489.
15. Ladel CH, Szalay G, Riedel D, Kaufmann SH. Interleukin-12 secretion by Mycobacterium tuberculosis-infected macrophages. Infect Immun. 1997;65:1936-1938.
16. Serbina NV, Flynn JL. Early Emergence of CD8+ T Cells Primed for Production of Type 1 Cytokines in the Lungs of Mycobacterium tuberculosis-Infected Mice. Kaufmann SHE, ed. Infect Immun. 1999;67:3980-3988.
17. Yu K, Mitchell C, Xing Y, Magliozzo RS, Bloom BR, Chan J. Toxicity of nitrogen oxides and related oxidants on mycobacteria: M. tuberculosis is resistant to peroxynitrite anion. Tuber Lung Dis. 1999;79(4):191-198.
18. Scanga CA, Mohan VP, Yu K, et al. Depletion of Cd4+ T Cells Causes Reactivation of Murine Persistent Tuberculosis despite Continued Expression of Interferon γ and Nitric Oxide Synthase 2. J Exp Med. 2000;192:347-358.
19. Vital Reyes VS, Téllez Velasco S, Hinojosa Cruz JC, Ortiz Romero Mde J, ChavarríaOlarte ME, Reyes Fuentes A. Serum levels of IL-1beta, IL-6 and TNF-alpha in infertile patients with ovarian dysfunction. GynecolObstet Mex. 2005;73:604-610.
20. El-Far M, El-Sayed IH, El-Motwally AE, Hashem IA, Bakry N. Serum levels of TNF-alpha and antioxidant enzymes and placental TNF-alpha expression in unexplained recurrent spontaneous miscarriage. J PhysiolBiochem. 2009;65:175–181.
21. Hollis BW, Wagner CL. Vitamin D deficiency during pregnancy: an ongoing epidemic. Am J Clin Nutr. 2006; 84:273.
22. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J,et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323-e333.
23. Sugarman J, Colvin C, Moran AC, Oxlade O. Tuberculosis in pregnancy: an
estimate of the global burden of disease. Lancet Glob Health. 2014;2(12):e710-e716.
24. Mathad JS, Gupta A. Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps. Clin Infect Dis. 2012;55:1532–1549.
25. Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, et al. IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007 Jun 1;178(11):7190-8. Erratum in: J Immunol. 2007;179(12):8569-8570.
26. Kindler V, Sappino AP, Grau GE, Piguet PF, Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989;56(5):731-740.
27. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Valle HBD, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56070/ doi: 10.17226/13050
28. ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy. Obstet Gynecol. 2011;118:197-198.
29. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Oct;26:2341-2357.
30. Wagner CL, McNeil R, Hamilton SA, Winkler J, Rodriguez Cook C, Warner G, Bivens B, Davis DJ, Smith PG, Murphy M, Shary JR, Hollis BW. A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina. Am J Obstet Gynecol. 2013 Feb;208:137.e1-13.
31. Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, et al. Maternal
vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal
study. Lancet.2006;367:36–43.
32. Farrant HJ, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, Osmond C, Veena SR, Fall CH. Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size. Eur J ClinNutr. 2009 May;63:646-652.
33. Agarwal N, Arya SC. Vitamin D3 Levels in Pregnant Women and Newborns at a Private Tertiary Care Hospital in Delhi, India. Int J Gynecol Obstet. 2011; 113, 240-241.
34. Marwaha RK, Tandon N, Chopra S, Agarwal N, Garg MK, Sharma B, Kanwar RS, Bhadra K, Singh S, Mani K, Puri S. Vitamin D status in pregnant Indian women across trimesters and different seasons and its correlation with neonatal serum 25-hydroxyvitamin D levels. Br J Nutr. 2011;106:1383-1389.
35. Clark DA, Arck PC, Chaouat G. Why did your mother reject you? Immunogenetic determinants of the response to environmental selective pressure expressed at the uterine level. Am J ReprodImmunol. 1999;41:5-22.
36. Raghupathy R. Pregnancy: Success and failure within the Th1/Th2/Th3 paradigm. SeminImmunol. 2001;13:219–227
37. Kupferminc MJ, Peaceman AM, Aderka D, Wallach D, Socol ML. Soluble tumor necrosis factor receptors and interleukin-6 levels in patients with severe preeclampsia. Obstet Gynecol.1996; 88:420-427.
38. Teran E, Escudero C, Moya W, Flores M, Vallance P, Lopez-Jaramillo P. Elevated C-reactive protein and pro-inflammatorycytokines in Andean women with preeclampsia. Int J Gynecol Obstet.2001; 75:243-249.
39. Hill JA, Devoe LD, Bryans CI Jr. Frequency of asymptomatic bacteriuria in preeclampsia. Obstel Gynecol.1986, 67:529-532.
40. Hsu CD, Witter FR. Urogenital infection in preeclampsia. Int J GynecolObstel.1995; 49:271-275.
41. Afshari JT, Ghomian N, Shameli A, Shakeri MT, Fahmidehkar MA, Mahajer E, et al. Determination of Interleukin-6 and Tumor Necrosis Factor-alpha concentrations in Iranian-Khorasanian patients with preeclampsia. BMC Pregnancy Childbirth. 2005 Nov 1;5:14.
42. van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid BiochemMol Biol. 2005;97:93–101.
43. Cantorna MT, Woodward WD, Hayes CE, DeLuca HF. 1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. J Immunol. 1998;160:5314–5319.
44. Zhu Y, Mahon BD, Froicu M, Cantorna MT. Calcium and 1 alpha, 25-dihydroxyvitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease. Eur J Immunol. 2005;35:217–224.
45. Lemire JM. Immunomodulatory role of 1, 25-dihydroxyvitamin D3. J Cell Biochem. 1992;49:26–31.
46. Azizieh F, Alyahya KO, Raghupathy R. Association between levels of vitamin D and inflammatory markers in healthy women. J Inflamm Res. 2016;9:51-57.
Published
2019-11-08
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