Status of vitamin D, antimicrobial peptide cathelicidin and T helper‑associated cytokines in patients with diabetes mellitus and pulmonary tuberculosis

Zhan,Yunfei; Jiang,Ling

doi:10.3892/etm.2014.2042

Status of vitamin D, antimicrobial peptide cathelicidin and T helper‑associated cytokines in patients with diabetes mellitus and pulmonary tuberculosis

Authors:
- Yunfei Zhan
- Ling Jiang
View Affiliations

Affiliations: Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: October 31, 2014 https://doi.org/10.3892/etm.2014.2042
Pages: 11-16

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Pulmonary tuberculosis (PTB) is a high burden infectious disease in China. The immune function is damaged in patients with diabetes mellitus (DM) who are easy to infect with Mycobacterium tuberculosis (Mtb). The growth of Mtb has been shown to be restrained following the administration of vitamin D and antimicrobial peptide cathelicidin (LL‑37); however, the effect in patients with DM and PTB remains unclear. Vitamin D can regulate the immune system through Vitamin D receptors expressed in T helper (Th) cells. The aim of the present study was to analyze the status and correlations of vitamin D, LL‑37 and Th‑associated cytokines in patients with PTB or PTB with DM (DMPTB). Serum 25‑hydroxyvitamin D3 [25(OH)D3] levels were measured by liquid chromatography‑tandem mass spectrometry, while plasma LL-37 levels were analyzed using a solid‑phase enzyme‑linked immunosorbent assay. Flow cytometry was used to analyze the levels of Th cytokines, including Th1‑associated IFN‑γ, Th2‑associated IL‑4 and Th17‑associated IL‑17. The results revealed that patients with PTB and DMPTB were vitamin D deficient or had insufficient vitamin D levels. Furthermore, the levels of LL‑37, IFN‑γ, IL‑4 and IL‑17 were higher in the PTB and DMPTB groups when compared with the normal controls. These results indicated that vitamin D supplementation is necessary for PTB and DMPTB patients. In addition, LL‑37, IFN‑γ and IL‑17 may be diagnostic indexes that become elevated in the compensatory response caused by Mtb infection. Vitamin D can regulate the immune status in patients suffering from PTB.

View Figures

View References

1	O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ and Berry MP: The immune response in tuberculosis. Annu Rev Immunol. 31:475–527. 2013. View Article : Google Scholar
2	Zuñiga J, Torres-García D, Santos-Mendoza T, Rodriguez-Reyna TS, Granados J and Yunis EJ: Cellular and humoral mechanisms involved in the control of tuberculosis. Clin Dev Immunol. 2012:1939232012. View Article : Google Scholar : PubMed/NCBI
3	Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G and He J: China National Diabetes and Metabolic Disorders Study Group: Prevalence of diabetes among men and women in China. N Engl J Med. 362:1090–1101. 2010. View Article : Google Scholar : PubMed/NCBI
4	Friis H, Range N, Pedersen ML, Mølgaard C, Changalucha J, Krarup H, Magnussen P, Søborg C and Andersen AB: Hypovitaminosis D is common among pulmonary tuberculosis patients in Tanzania but is not explained by the acute phase response. J Nutr. 138:2474–2480. 2008. View Article : Google Scholar : PubMed/NCBI
5	Arnedo-Pena A, Juan-Cerdán JV, Romeu-Garcia A, Garcia-Ferrer D, Holguín-Gómez R, Iborra-Millet J, Herrero-Carot C, Piñana MJ, Bellido-Blasco J, Ferrero-Vega JA, Adsuara LS, Silvestre ES, Ferrer NM and Bartual VR: Latent tuberculosis infection, tuberculin skin test and vitamin D status in contacts of tuberculosis patients: a cross-sectional and case-control study. BMC Infect Dis. 11:3492011. View Article : Google Scholar : PubMed/NCBI
6	Chun RF, Adams JS and Hewison M: Immunomodulation by vitamin D: implications for TB. Expert Rev Clin Pharmacol. 4:583–591. 2011. View Article : Google Scholar : PubMed/NCBI
7	Cadranel J, Garabedian M, Milleron B, Guillozo H, Akoun G and Hance AJ: 1,25(OH)₂D₂ production by T lymphocytes and alveolar macrophages recovered by lavage from normocalcemic patients with tuberculosis. J Clin Invest. 85:1588–1593. 1990. View Article : Google Scholar : PubMed/NCBI
8	Baeke F, Takiishi T, Korf H, Gysemans C and Mathieu C: Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 10:482–496. 2010. View Article : Google Scholar : PubMed/NCBI
9	Desai NS, Tukvadze N, Frediani JK, Kipiani M, Sanikidze E, Nichols MM, Hebbar G, Kempker RR, Mirtskhulava V, Kalandadze I, Seydafkan S, Sutaria N, Chen TC, Blumberg HM, Ziegler TR and Tangpricha V: Effects of sunlight and diet on vitamin D status of pulmonary tuberculosis patients in Tbilisi, Georgia. Nutrition. 28:362–366. 2012. View Article : Google Scholar : PubMed/NCBI
10	Choi HS, Kim KA, Lim CY, Rhee SY, Hwang YC, Kim KM, Kim KJ, Rhee Y and Lim SK: Low serum vitamin D is associated with high risk of diabetes in Korean adults. J Nutr. 141:1524–1528. 2011. View Article : Google Scholar : PubMed/NCBI
11	Chagas CE, Borges MC, Martini LA and Rogero MM: Focus on vitamin D, inflammation and type 2 diabetes. Nutrients. 4:52–67. 2012. View Article : Google Scholar : PubMed/NCBI
12	Dalgård C, Petersen MS, Weihe P and Grandjean P: Vitamin D status in relation to glucose metabolism and type 2 diabetes in septuagenarians. Diabetes Care. 34:1284–1288. 2011. View Article : Google Scholar : PubMed/NCBI
13	Biyoudi-Vouenze R, Cadranel J, Valeyre D, Milleron B, Hance AJ and Soler P: Expression of 1,25(OH)₂D₃ receptors on alveolar lymphocytes from patients with pulmonary granulomatous diseases. Am Rev Respir Dis. 143:1376–1380. 1991. View Article : Google Scholar : PubMed/NCBI
14	Kota SK, Jammula S, Kota SK, Tripathy PR, Panda S and Modi KD: Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis. Diabetes Metab Syndr. 5:85–89. 2011. View Article : Google Scholar : PubMed/NCBI
15	Yamshchikov AV, Kurbatova EV, et al: Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis. Am J Clin Nutr. 92:603–611. 2010. View Article : Google Scholar : PubMed/NCBI
16	Rivas-Santiago B, Rivas, Santiago CE, Castañeda-Delgado JE, León-Contreras JC, Hancock RE and Hernandez-Pando R: Activity of LL-37, CRAMP and antimicrobial peptide-derived compounds E2, E6 and CP26 against Mycobacterium tuberculosis. Int J Antimicrob Agents. 41:143–148. 2013. View Article : Google Scholar
17	Martineau AR, Newton SM, Wilkinson KA, Kampmann B, Hall BM, Nawroly N, Packe GE, Davidson RN, Griffiths CJ and Wilkinson RJ: Neutrophil-mediated innate immune resistance to mycobacteria. J Clin Invest. 117:1988–1994. 2007. View Article : Google Scholar : PubMed/NCBI
18	Vidyarani M, Selvaraj P, Jawahar MS and Narayanan PR: 1,25 Dihydroxyvitamin D₃ modulated cytokine response in pulmonary tuberculosis. Cytokine. 40:128–134. 2007. View Article : Google Scholar : PubMed/NCBI
19	Okamoto Yoshida Y, Umemura M, et al: Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J Immunol. 184:4414–4422. 2010. View Article : Google Scholar : PubMed/NCBI
20	Umemura M, Yahagi A, Hamada S, et al: IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol. 178:3786–3796. 2007. View Article : Google Scholar : PubMed/NCBI
21	Salahuddin N, Ali F, Hasan Z, Rao N, Aqeel M and Mahmood F: Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis’. BMC Infect Dis. 13:222013. View Article : Google Scholar
22	Rathored J, Sharma SK, Singh B, et al: Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D. Int J Tuberc Lung Dis. 16:1522–1528. 2012. View Article : Google Scholar : PubMed/NCBI
23	Mily A, Rekha RS, Kamal SM, Akhtar E, Sarker P, Rahim Z, Gudmundsson GH, Agerberth B and Raqib R: Oral intake of phenylbutyrate with or without vitamin D₃ upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis. BMC Pulm Med. 13:232013. View Article : Google Scholar
24	Selvaraj P, Harishankar M, Singh B, Banurekha VV and Jawahar MS: Effect of vitamin D₃ on chemokine expression in pulmonary tuberculosis. Cytokine. 60:212–219. 2012. View Article : Google Scholar : PubMed/NCBI
25	Prabhu Anand S, Selvaraj P and Narayanan PR: Effect of 1,25 dihydroxyvitamin D₃ on intracellular IFN-gamma and TNF-alpha positive T cell subsets in pulmonary tuberculosis. Cytokine. 45:105–110. 2009. View Article : Google Scholar
26	Kumar NP, Sridhar R, Banurekha VV, Jawahar MS, Nutman TB and Babu S: Expansion of pathogen-specific T-helper 1 and T-helper 17 cells in pulmonary tuberculosis with coincident type 2 diabetes mellitus. J Infect Dis. 208:739–748. 2013. View Article : Google Scholar : PubMed/NCBI
27	Yu Y, Zhang Y, Hu S, Jin D, Chen X, Jin Q and Liu H: Different patterns of cytokines and chemokines combined with IFN-γ production reflect Mycobacterium tuberculosis infection and disease. PLoS One. 7:e449442012. View Article : Google Scholar
28	Whitworth HS, Scott M, Connell DW, Dongés B and Lalvani A: IGRAs - the gateway to T cell based TB diagnosis. Methods. 61:52–62. 2013. View Article : Google Scholar : PubMed/NCBI
29	Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, Packe GE, Moore-Gillon JC, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Woodward NJ, Venton TR, Barnes KE, Mullett CJ, Coussens AK, Rutterford CM, Mein CA, Davies GR, Wilkinson RJ, Nikolayevskyy V, Drobniewski FA, Eldridge SM and Griffiths CJ: High-dose vitamin D₃ during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 377:242–250. 2011. View Article : Google Scholar : PubMed/NCBI