Summary
To evaluate the role of zinc status in immune system dysfunction in diabetic animals, the interleukin-2 production and the lymphocyte mitogenic response to phytohaemagglutinin, concanavalin A and lipopolysaccharide were measured in streptozotocin-induced diabetic rats, diabetic rats treated with insulin and their non-diabetic controls maintained on low zinc, normal zinc and high zinc diets for 3 weeks. Unstimulated lymphocyte proliferation was significantly lower in diabetic rats compared to nondiabetic control rats maintained on normal zinc diet (1505±318 vs 3447±497 cpm) (p<0.005) or low zinc diet (546±191 vs 4011±628cpm) (p<0.005). High zinc diet attenuated the difference between the diabetic rats (2404±833 cpm) and control rats (3929±713 cpm). Insulinised diabetic rats were similar to control rats. Phytohaemagglutinin-stimulated lymphocyte proliferation was not significantly altered with dietary zinc changes, but diabetic rats on low zinc diet had significantly lower (p<0.025) values compared to control rats on the same diet (41470±7874 vs 72308±8895 cpm). Insulinisation did not normalise phytohemaegglutinin-stimulated lymphocyte proliferation (40711±3666 cpm). Similarly, cells from diabetic rats on low zinc diet, unlike their controls, failed to respond to concanavalin A stimulation. Compared to control rats the diabetic rats on either low or normal zinc diets had lower lipopolysaccharide-stimulated lymphocyte proliferation. High zinc diet or insulinisation normalised mitogenic response of lymphocytes to lipopolysaccharide. Unlike the diabetic rats alterations in dietary zinc intake did not significantly affect the lymphocyte proliferation in control rats. Neither the diabetic state nor zinc status had any significant effect on interleukin-2 production. Thus, zinc status of the animal is an important determinant of cell-mediated immunity, but additional factors peculiar to the diabetic state may be involved in the modulation of the immune system in diabetes.
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References
Fairchild RS, Kyner JL, Abdou NI (1982) Specific immunoregulation abnormality in insulin dependent diabetes mellitus. J Lab Clin Med 99: 175–185
Chandy KG, Charles AM, Kershnar A, Buckingham B, Waldeck N, Gupta S (1984) Autologous mixed lumphocyte reaction in man XV. Cellular and molecular basis of deficient autologous mixed lymphocyte response in insulin-dependent diabetes mellitus. J Clin Immunol 4: 424–428
Zier KS, Leo MM, Spielman RS, Baker L (1984) Decreased synthesis of interleukin-2 (IL2) in insulin dependent diabetes mellitus. Diabetes 33(6): 552–555
Galluzzo A, Giordano C, Rubino G, Bompiani GD (1984) Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 26: 426–430
FoVenyi J, Totpal K, Thaisz E, Garam T (1984) Nonspecific cellular immunity in Type 1 and Type 2 diabetes. Exp Clin Endocrinol 83: 203–206
Herold KC, Huen A, Gould L, Traisman H, Rubenstein AH (1984) Alterations in lymphocyte subpopulations in Type 1 (insulin dependent) diabetes mellitus: exploration of possible mechanisms and relationships to autoimmune phenomena. Diabetologia 27: 102–105
Duchateau J, Delespesse G, Vareake P (1981) Influence of oral zinc supplementation on the lymphocyte response to mitogens of normal subjects. Am J Clin Nutr 34: 88–93
Blazsek I, Mathe G (1984) Zinc and immunity. Biomed Pharmacother 38: 187–193
Beisel WR (1982) Single nutrients and immunity. Am J Clin Nutr 35: 417–468
Mooradian AD, Morley JE (1987) Micronutrient status in diabetes mellitus. Am J Clin Nutr 45: 877–895
Duchateau J, Delepesse G, Vrijens R, Collet H (1981) Beneficial effects of oral zinc supplementation on the immune response of old people. Am J Med 70: 1001–1004
Steidemann M, Harrell I (1980) Relation of immunocompetence to selected nutrients in elderly women. Nutr Rep Int 21: 931–940
Allen JI, Perri RT, McClain EJ, Kay NE (1983) Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. J Lab Clin Med 102: 577–589
Fernandes G, Nair M, Onoe K, Tanaka T, Floyd R, Good RA (1979) Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice. Proc Natl Acad Sci USA 76: 457–461
Allen JL, Bell E, Boosalis MG, Oken MM, McClain CJ, Levine AS, Morley JE (1985) Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung cancer. Am J Med 79: 209–215
Niewoehner CB, Allen JI, Boosalis M, Levine AS, Morley JE (1986) Role of zinc supplementation in Type 2 diabetes mellitus. Am J Med 81: 63–68
Lawrence S, Charlesworth JA, Pussell BA, Campbell LV, Kotowicz MA (1986) Factors influencing reticulophagocytic function in insulin-treated diabetes. Diabetes 33: 813–818
Donaldson DL, Kubo C, Smith CC, Good RA (1986) Effects of genetic diabetes and zinc nutriture on in vivo cell-mediated immunity in the mouse. Am J Clin Nutr 43: 263–271
Mahmoud AAF, Rodman HM, Mandel MA, Warren KS (1976) Induced and spontaneous diabetes mellitus and suppression of cell mediated immunologic responses. J Clin Invest 57: 362–367
Fernandes G, Handwerger BS, Yunis EJ, Brown DM (1978) Immune response to the mutant diabetic C57BL/KS-db +mouse. J Clin Invest 61: 243–250
Roth MD, Barg M, Michalski R, Arquilla R (1980) Cell mediated immunity in chronically diabetic mice. Diabetes 29: 825–829
Chi DS, Berry DL, Dillon KA, Arbogast BW (1982) Inhibition of in vitro lymphocyte response by streptozotocin — induced diabetic rat serum: a function of very low density lipoproteins. Diabetes 31: 1098–1104
Deebaj L, Song MK, Mooradian AD (1988) The effect of dietary zinc content on micronutrient status of control and diabetic rats. Clin Res 36: 96 A
James SJ, Swendseid M, Makinodan T (1987) Macrophage mediated depression of T-cell proliferation in zinc deficient mice. J Nutr 117: 1982–1988
Chang MP, Makinodan T, Peterson WJ, Strehler B (1982) Role of T-cells and adherent cells in age-related decline in murine interleukin-2 production. J Immunol 129: 2426–2430
Gillis S, Form MM, Ou W, Smith KA (1978) T-cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol 120: 2027–2032
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Mooradian, A.D., Norman, D.C. & Morley, J.E. The effect of zinc status on the immune function of diabetic rats. Diabetologia 31, 703–707 (1988). https://doi.org/10.1007/BF00278755
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DOI: https://doi.org/10.1007/BF00278755