Abstract
Background: Serum 25-hydroxy vitamin D (S-25(OH) D), in pulmonary Tubercular patient enhances host protective immune response to mycobacterium tuberculosis (TB) and reduces disease associated inflammation. The aim of present study is to evaluate correlation between S-25(OH) D levels, Body mass index (BMI) and albumin in drug induced hepatotoxicity (DIH) under Directly Observed Therapy Short course (DOTS) treatment.
Methods: Total of 107 (70 male, 37 female) age-sex matched pulmonary TB control and 58 (38 male, 20 female) DIH patients, age grouped 20-70 years, were included in the study. Anthropometric measurements, Liver function test (LFT), S-25(OH)D, biochemical, radiological and microbial markers were computed. Biochemical marker assessment was performed on 1st, 4th, 8th and 16th week in all study patients and P-values by unpaired t test of various parameters obtained on 1st and 16th week were calculated.
Results: The comparative study of S-25(OH)D, Albumin and BMI in control TB and DIH patient under ATT on 1st and 16th week showed significant differences. DIH patients showed S-25(OH)D level deficient (less than 20 ng/ml) in comparison to non-DIH patient insufficient value (20-29 ng/ml) under chemotherapy (P < 0.0001). BMI was found less in DIH patients than control but the statistics were insignificant (P < 0.118). Hypoalbuminemia was seen in DIH patient where as control albumin levels were in baseline (P < 0.039).
Conclusions: The pulmonary TB patients having DIH should be supplied with higher doses of S-25(OH)D to accelerate the radiological and immunological recovery as deficient levels of vitamin D worsen the severity of infection.
Keywords: Tuberculosis, S-25(OH)D, Innate immunity, Immuno-modulatory activity, Drug Induced Hepatotoxicity.
References
1. Tuberculosis control in the South-East Asia Region. Epidemiology, strategy, financing: WHO, Regional Office for South-East Asia, Annual report 2015; 1 & 195.
2. Senousy BE, Belal SI, Draganov PV. Hepatotoxic effects of therapies for tuberculosis. Nat Rev Gastroenterol Hepatol. 2010; 7:543–56.
3. Parasher I, Nagtilak S, Jha A, Kumar N et al. Anti-tubercular drug induced hepatotoxicity: associated risk factors under rntcp-dots pulmonary tuberculosis patients. Int. J. Adv. Res. 2016; 4(8), 1372-1376.
4. Asati A, Indurkar M. Profile of Adverse Drug Reactions in TB Patients Taking ATT. J Med Sci Clin Res. 2016; 4(12): 14589-14592.
5. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–281.
6. Hewison M. Vitamin D and innate and adaptive immunity. Vitam Horm. 2011; 86: 24-62.
7. Hewison M. An update on vitamin D and human immunity. Clinical Endocrinology. 2012; 76, 315–325.
8. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q et al. Cutting edge: 1, 25- dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004; 173:2909-2912.
9. Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system:modulation of innate and autoimmunity. J Mol Med (Berl). 2010; 88: 441–450.
10. Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L. Regulatory T cells induced by 1 alpha, 25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol. 2001; 167:1945-1953.
11. Takeyama K, Kitanaka S, Sato T, Kobori M, Yanagisawa J, Kato S. 25- Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science. 1997; 277:1827–30.
12. Jones G, Prosser DE, Kaufmann M. 25-Hydroxyvitamin D-24-hydroxylase (CYP2-4A1): its important role in the degradation of vitamin D. Arch Biochem Biophys. 2012; 523:9-18.
13. Adorini L. Intervention in autoimmunity: The potential of vitamin D receptor agonists. Cellular Immunology. 2005; 233:115–124.
14. Penna G, Roncari A, Amuchastegui S, Daniel KC, Berti E et al. Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1, 25-dihydroxyvitamin D3. Blood. 2005;106:3490–3497.
15. Adorini L. Tolerogenic Dendritic Cells Induced by Vitamin D Receptor Ligands Enhance Regulatory T Cells Inhibiting Autoimmune Diabetes. Ann. N.Y. Acad. Sci. 2003; 987: 258-26.
16. Holick MF, Binkley NC et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline; J Clin Endocrine Metab. 2011; 96 (7):1911-1930.
17. Ralph AP, Kelly PM, Anstey NM. L-arginine and vitamin D: novel adjunctive immunotherapies in tuberculosis. Trends Microbiol. 2008;16:336-344.
18. Holick MF, Chen TC et al. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S-1086S.
19. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D–mediated human antimicrobial response. Science. 2006; 311:1770-1773.
20. Boonstra A, Basrat FJ, Crain C, Heath VI, Savel koul HF, D ‘Garra A, Alfa 25- Dihydroxy vitamin d3 has a direct effect on naïve CD4(+)T Cells to enhance the development of Th2 cells. J. Immunol. 2001; 167 (4): 4974-4980.
21. Lin PL, Flynn JI. Understanding latent tuberculosis: a moving target. J. Immunol. 2010; 185 (1): 15-22.
22. Coussens AK, Wilkinson RJ et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatm-ent.AR. Proc Natl Acad Sci USA 2012; 109(38):15449–15454.
DOI: https://dx.doi.org/10.18535/jmscr/v5i5.119
