Alteration in T-Cell Cytokine Production by Vitamin A and Zinc Supplementation in Mice

DOI: 10.4236/fns.2012.38141   PDF   HTML     2,860 Downloads   4,729 Views   Citations

Abstract

Simultaneous zinc and vitamin A deficiency are common health problems in developing countries. The objective of this study was to assess effect of supplementation of high zinc or vitamin A on immune function. After three months of feeding with a zinc and vitamin A deficient diet, mice were assigned into four groups which, for additional two months, received a normal or high zinc along with vitamin A deficient diet and a normal or high vitamin A along with zinc deficient diet. Serum and intestinal mucosa immunoglobulin A (IgA) were determined and supernatants of splenocytes were used to assess interlukin (IL)-2, IL-5, IFN-γ. Mice maintained on zinc deficient diet with normal or high vitamin A resulted in significantly lower production of IFN-γ. Also, supplementation of high dose vitamin A augmented production of the cytokine as compared to normal intake of the vitamin. Supplementation of either normal or high zinc along with low vitamin A diet significantly led to higher production of IFN-γ as compared to those receiving zinc limited but adequate vitamin A. High intake of zinc along with vitamin A deficient diet significantly enhanced secretion of IL-2. Levels of serum and mucosal IgA and IL-5 were not be significantly modulated. Moreover, animals fed with high doses of zinc showed increased IL-2 production than those that had normal intake of zinc. Results indicated that zinc and vitamin A supplementation up-regulates production of T-cell cytokines, IFN-γ and IL-2.

Share and Cite:

S. Kheirvari and M. Alizadeh, "Alteration in T-Cell Cytokine Production by Vitamin A and Zinc Supplementation in Mice," Food and Nutrition Sciences, Vol. 3 No. 8, 2012, pp. 1060-1067. doi: 10.4236/fns.2012.38141.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] C. P. Wong, Y. Song, V. D. Elias, K. R. Magnusson and E. Ho, “Zinc Supplementation Increases Zinc Status and Thymopoiesis in Aged Mice,” The Journal of Nutrition, Vol. 139, No. 7, 2009, pp. 1393-1397. doi:10.3945/jn.109.106021
[2] L. Alappat, M. Valerio and A. B. Awad, “Effect of Vitamin D and β-Sitosterol on Immune Function of Macrophages,” International Immunopharmacology, Vol. 10, No. 11, 2010, pp. 1390-1396. doi:10.1016/j.intimp.2010.08.003
[3] T. Treadwell, “Commentary: Enhanced Healing of Surgical Wounds of the Lower Leg Using Weekly Zinc Oxide Compression Dressings,” Dermatologic Surgery, Vol. 37, No. 2, 2011, pp. 166-167.
[4] M. D. Lastra, R. Pastelin, A. Camacho, B. Monroy and A. E. Aguilar, “Zinc Intervention on Macrophages and Lymphocytes Response,” Journal of Trace Elements in Medicine and Biology, Vol. 15, No. 1, 2001, pp. 5-10. doi:10.1016/S0946-672X(01)80019-5
[5] R. A. Winchurch, J. Togo and W. H. Adler, “Supplemental Zinc Restores Antibody Formation in Cultures of Aged Spleen Cells. III. Impairment of II-2-Mediated Responses,” Clinical Immunology and Immunopathology, Vol. 49, No. 2, 1988, pp. 215-222.
[6] B. Bao, A. S. Prasad, F. W. Beck and M. Godmere, “Zinc Modulates mRNA Levels of Cytokines,” American Journal of Physiology—Endocrinology and Metabolism, Vol. 285, No. 5, 2003, pp. E1095-1102.
[7] S. L. Jensen, C. McCuaig, A. Zembowicz and M. A. Hurt, “Bullous Lesions in Acrodermatitis Enteropathica Delaying Diagnosis of Zinc Deficiency: A Report of Two Cases and Review of the Literature,” Journal of Cutaneous Pathology, Vol. 35, Suppl. 1, 2008, pp. 1-13. doi:10.1111/j.1600-0560.2008.00981.x
[8] C. T. Walsh, H. H. Sandstead, A. S. Prasad, P. M. Newberne and P. J. Fraker, “Zinc Health Effects and Research Priorities for the 1990’s,” Environmental Health Perspectives, Vol. 102, Suppl. 2, 1994, pp. 5-46. doi:10.2307/3431820
[9] P. D. Zalewski, “Zinc and Immunity: Implications for Growth, Survival and Function of Lymphoid Cells,” Journal of Nutritional Immunology, Vol. 4, No. 3, 1996, pp. 39-101.
[10] Z. Karakas, N. Demirel, M. Tarakcioglu and N. Mete, “Serum Zinc and Copper Levels in Southeastern Turkish Children with Giardiasis or Amebiasis,” Biological Trace Element Research, Vol. 84, No. 1-3, 2001, pp. 11-18. doi:10.1385/BTER:84:1-3:011
[11] M. E. Penny, J. M. Peerson, R. M. Marin, A. Duran, C. F. Lanara, B. Lonnerdal, R. E. Black and R. H. Brown, “Randomized, Community-Based Trial of the Effect of Zinc Supplementation, with and without Other Micronutrients, on the Duration of Persistent Childhood Diarrhea in Lima. Peru,” Journal of Pediatric, Vol. 135, No. 2, 1999, pp. 208-217. doi:10.1016/S0022-3476(99)70024-7
[12] W. Zhong, C. J. McClain, M. Cave, Y. J. Kang and Z. Zhou, “The Role of Zinc Deficiency in Alcohol-Induced Intestinal Barrier Dysfunction,” American Journal of Physiology—Endocrinology and Metabolism, Vol. 298, No. 5, 2010, pp. G625-633. doi:10.1152/ajpgi.00350.2009
[13] S. Southon, G. Livesey, J. M. Gee and I. T. Johnson, “Intestinal Cellular Proliferation and Protein Synthesis in Zinc-Deficient Rats,” British Journal of Nutrition, Vol. 53, No. 1, 1985, pp. 595-603. doi:10.1079/BJN19850013
[14] B. Vallee and K. H. Falchuk, “The Biochemical Basis of Zinc,” Physiological Reviews, Vol. 73, No. 1, 1993, pp. 79-118.
[15] A. Ertesvag, H. C. Aasheim, S. Naderi and H. K. Blomhoff, “Vitamin A Potentiates CpG-Mediated Memory B-Cell Proliferation and Differentiation: Involvement of Early Activation of p38MAPK,” Blood, Vol. 109, No. 9, 2007, pp. 3865-3872. doi:10.1182/blood-2006-09-046748
[16] J. A. Hall, J. L. Cannons, J. R. Grainger, L. M. Dos Santos, T. W. Hand, S. Naik, E. A. Wohlfert, D. B. Chou, G. Oldenhove, M. Robinson, M. E. Grigg, R. Kastenmayer, P. L. Schwartzberg and Y. Belkaid, “Essential Role for Retinoic Acid in the Promotion of CD4(+) T Cell Effector Responses via Retinoic Acid Receptor Alpha,” Immunity, Vol. 34, No. 3, 2011, pp. 435-447. doi:10.1016/j.immuni.2011.03.003
[17] P. Aukrust, F. Muller, T. Ueland, et al., “Decreased Vitamin A Levels in Common Variable Immunodeficiency: Vitamin A Supplementation in Vivo Enhances Immunoglobulin Production and Down Regulates Inflammatory Responses,” European Journal of Clinical Investigation, Vol. 30, No. 3, 2000, pp. 252-259. doi:10.1046/j.1365-2362.2000.00619.x
[18] K. A. Hoag, F. E. Nashold, J. Goverman and C. E. Hayes, “Retinoic Acid Enhances the T Helper 2 Cell Development That Is Essential for Robust Antibody Responses through Its Action on Antigen-Presenting Cells,” The Journal of Nutrition, Vol. 132, No. 12, 2002, pp. 3736- 3739.
[19] C. K. Park, Y. Ishimi, M. Ohmura, M. Yamaguchi and S. Ikegami, “Vitamin A and Carotenoids Stimulate Differentiation of Mouse Osteoblastic Cells,” Journal of Nutritional Science and Vitaminology, Vol. 43, No. 3, 1997, pp. 281-296. doi:10.3177/jnsv.43.281
[20] H. K. Blomhoff and E. B. Smeland, “Role of Retinoids in Normal Hematopoiesis and in the Immune System,” In: R. Blomhoff, Ed., Vitamin A in Health and Disease, Marcel Dekker, New York, 1994, p. 451.
[21] Q. Chen and A. C. Ross, “Vitamin A and Immune Function: Retinoic Acid Modulates Population Dynamics in Antigen Receptor and CD38-Stimulated Splenic B Cells,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 40, 2005, pp. 14142-14149. doi:10.1073/pnas.0505018102
[22] C. Cameron, F. Dallaire, C. Vézina, G. Muckle, S. Bruneau, P. Ayotte and E. Dewailly, “Neonatal Vitamin A Deficiency and Its Impact on Acute Respiratory Infections among Preschool Inuit Children,” Canadian Journal of Public Health, Vol. 99, No. 2, 2008, pp. 102-106.
[23] A. Imdad, M. Y. Yakoob, C. Sudfeld, B. A. Haider, R. E. Black and Z. A. Bhutta, “Impact of Vitamin A Supplementation on Infant and Childhood Mortality,” BMC Public Health, Vol. 11, Suppl. 3, 2011, p. S20. doi:10.1186/1471-2458-11-S3-S20
[24] P. Donnen, A. Sylla, M. Dramaix, G. Sall, N. Kuakuvi and P. Hennart, “Effect of Daily Low Dose of Vitamin A Compared with Single High Dose on Morbidity and Mortality of Hospitalized Mainly Malnourished Children in Senegal: A Randomized Controlled Clinical Trial,” European Journal of Clinical Nutrition, Vol. 61, No. 12, 2007, pp. 1393-1399. doi:10.1038/sj.ejcn.1602671
[25] A. Imdad, K. Herzer, E. Mayo-Wilson, M. Y. Yakoob and Z. A. Bhutta, “Vitamin A Supplementation for Preventing Morbidity and Mortality in Children from 6 Months to 5 Years of Age,” Cochrane Database of Systematic Reviews, Vol. 12, 2010, Article ID: CD008524.
[26] P. Christian and K. P. West Jr., “Interactions between Zinc and Vitamin A: An Update,” The American Journal of Clinical Nutrition, Vol. 68, Suppl. 2, 1998, pp. 435- 441.
[27] C. W. Levenson, “Zinc Regulation of Food Intake: New Insights on the Role of Neuropeptide Y,” Nutrition Reviews, Vol. 61, No. 7, 2003, pp. 247-249. doi:10.1301/nr.2003.jul.247-249
[28] L. M. Gaetke, R. C. Frederich, H. S. Oz and C. J. McClain, “Decreased Food Intake Rather than Zinc Deficiency Is Associated with Changes in Plasma Leptin, Metabolic Rate, and Activity Levels in Zinc Deficient Rats (Small Star, Filled),” The Journal of Nutritional Biochemistry, Vol. 13, No. 4, 2002, pp. 237-244. doi:10.1016/S0955-2863(01)00220-0
[29] I. S. Kwun, Y. E. Cho, R. A. Lomeda, S. T. Kwon, Y. Kim and J. H. Beattie, “Marginal Zinc Deficiency in Rats Decreases Leptin Expression Independently of Food Intake and Corticotrophin-Releasing Hormone in Relation to Food Intake,” The British Journal of Nutrition, Vol. 98, No. 3, 2007, pp. 485-489. doi:10.1017/S0007114507730763
[30] S. Moriguchi, L. Werner and R. R. Watson, “High Dietary Vitamin A (Retinyl Palmitate) and Cellular Immune Functions in Mice,” Immunology, Vol. 56, No. 1, 1985, pp. 169-177.
[31] R. Albers, M. Bol, R. Bleumink, A. A. Willems and R. H. Pieters, “Effects of Supplementation with Vitamins A, C, and E, Selenium, and Zinc on Immune Function in a Murine Sensitization Model,” Nutrition, Vol. 19, No. 11-12, 2003, pp. 940-946. doi:10.1016/S0899-9007(03)00178-3
[32] Y. Yang, Y. Yuan, Y. Tao and W. Wang, “Effects of Vitamin A Deficiency on Mucosal Immunity and Response to Intestinal Infection in Rats,” Nutrition, Vol. 27, No. 2, 2011, pp. 227-232. doi:10.1016/j.nut.2009.11.024
[33] C. B. Stephensen, Z. Moldoveanu and N. N. Gangopadhyay, “Vitamin A Deficiency Diminishes the Salivary Immunoglobulin A Response and Enhances the Serum Immunoglobulin G Response to Influenza A Virus Infection in BALB/c Mice,” The Journal of Nutrition, Vol. 126, No. 1, 1996, pp. 94-102.
[34] U. Wiedermann, L. A. Hanson, J. Holmgren, H. Kahu and U. I. Dahlgren, “Impaired Mucosal Antibody Response to Cholera Toxin in Vitamin A-Deficient Rats Immunized with Oral Cholera Vaccine,” Infection and Immunity, Vol. 61, No. 9, 1993, pp. 3952-3957.
[35] D. K. Chattopadhyay, C. R. Maity and D. J. Nag, “Effect of Zinc Supplementation on Mycospecific Immunoglobulins in Tuberculosis Patients,” Journal of the Indian Medical Association, Vol. 108, No. 2, 2010, pp. 92-93.
[36] T. Nikawa, K. Odahara, H. Koizumi, Y. Kido, S. Teshima, K. Rokutan and K. Kishi, “Vitamin A Prevents the Decline in Immunoglobulin A and Th2 Cytokine Levels in Small Intestinal Mucosa of Protein-Malnourished Mice,” The Journal of Nutrition, Vol. 129, No. 5, 1999, pp. 934- 941.
[37] C. B. Stephensen, R. Rasooly, X. Jiang, M. A. Ceddia, C. T. Weaver, R. A. Chandraratna and R. P. Bucy, “Vitamin A Enhances in Vitro Th2 Development via Retinoid X Receptor Pathway,” The Journal of Immunology, Vol. 168, No. 9, 2002, pp. 4495-4503.
[38] A. S. Prasad, “Effects of Zinc Deficiency on Th1 and Th2 Cytokine Shifts,” The Journal of Infectious Diseases, Vol. 182, Suppl. 1, 2000, pp. 62-68.
[39] A. S. Prasad, F. W. Beck, S. M. Grabowski, J. Kaplan and R. H. Mathog, “Zinc Deficiency: Changes in Cytokine Production and T-Cell Subpopulations in Patients with Head and Neck Cancer and in Noncancer Subjects,” Proceedings of the Association of American Physicians, Vol. 109, No. 1, 1997, pp. 68-77.
[40] Y. H. Tao and Y. Yang, “Effects of Vitamin A on the Differentiation, Maturation and Functions of Dendritic Cells from Cord Blood,” Chinese Journal of Pediatrics, Vol. 42, No. 5, 2004, pp. 340- 343.
[41] M. Iwata, Y. Eshima and H. Kagechika, “Retinoic Acids Exert Direct Effects on T Ells to Suppress Th1 Development and Enhance Th2 Development via Retinoic Acid Receptors,” International Immunology, Vol. 15, No. 8, 2003, pp. 1017-1025. doi:10.1093/intimm/dxg101
[42] X. Wu, X. Liu and J. Tang, “The Effect of Vitamin A on Secretion of IFN-Gamma and IL-4 in A549 Cells Induced by Mycoplasma Pneumoniae,” Journal of Huazhong University of Science and Technology-Medical Sciences, Vol. 28, No. 6, 2008, pp. 649-652. doi:10.1007/s11596-008-0607-6
[43] D. Cui, Z. Moldoveanu and C. B. Stephensen, “High- Level Dietary Vitamin A Enhances T-Helper Type 2 Cytokine Production and Secretory Immunoglobulin A Response to Influenza A Virus Infection in BALB/c Mice,” The Journal of Nutrition, Vol. 130, No. 5, 2000, pp. 1132-1139.
[44] L. M. Allende, A. Corell, A. Madrono, R. Gongora, C. Rodriguez-Gallego, A. Lopez-Goyanes, M. Rosal and A. Arnaiz-Villena, “Retinol (Vitamin A) Is a Cofactor in CD3-Induced Human T-Lymphocyte Activation,” Immunology, Vol. 90, No. 3, 1997, pp. 388-396. doi:10.1111/j.1365-2567.1997.00388.x
[45] N. Engedal, A. Ertesvag and H. K. Blomhoff, “Survival of Activated Human T Lymphocytes Is Promoted by Retinoic Acid Via Induction of IL-2,” International Immunology, Vol. 16, No. 3, 2004, pp. 443-453. doi:10.1093/intimm/dxh048
[46] H. K. Blomhoff, “Vitamin A Regulates Proliferation and Apoptosis of Human T- and B-Cells,” Biochemical Society Transactions, Vol. 32, No. 6, 2004, pp. 982-984.
[47] A. Ertesvag, N. Engedal, S. Naderi and H. K. Blomhoff, “Retinoic Acid Stimulates the Cell Cycle Machinery in Normal T Cells: Involvement of Retinoic Acid Receptor-Mediated IL-2 Secretion,” The Journal of Immunology, Vol. 169, No. 10, 2002, pp. 5555-5563.
[48] A. K. Baltaci, R. Mogulkoc, C. S. Bediz and A. Pekel, “Effects of Zinc Deficiency and Pinealectomy on Cellular Immunity in Rats Infected with Toxoplasma Gondii,” Biological Trace Element Research, Vol. 104, No. 1, 2005, pp. 47-56. doi:10.1385/BTER:104:1:047
[49] A. K. Baltaci, C. S. Bediz, R. Mogulkoc, E. Kurtoglu and A. Pekel, “Effect of Zinc and Melatonin Supplementation on Cellular Immunity in Rats with Toxoplasmosis,” Biological Trace Element Research, Vol. 96, No. 1-3, 2003, pp. 237-245. doi:10.1385/BTER:96:1-3:237
[50] A. S. Prasad, B. Bao, F. W. Beck and F. H. Sarkar, “Zinc Enhances the Expression of Interleukin-2 and Interleukin-2 Receptors in HUT-78 Cells by Way of NF- KappaB Activation,” Journal of Laboratory and Clinical Medicine, Vol.140, No. 4, 2002, pp. 272-289. doi:10.1067/mlc.2002.127908
[51] F. W. Beck, A. S. Prasad, J. Kaplan, J. T. Fitzgerald and G. J. Brewer, “Changes in Cytokine Production and T Cell Subpopulations in Experimentally Induced Zinc- Deficient Humans,” American Journal of Physiology, Vol. 272, No. 6, 1997, pp. E1002-E1007.

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.