Abstract
The studies reported here suggest that the immunomodulatory effects of 1,1-dimethylhydrazine (UDMH) are associated, in part, with interference with interleukin 2 (IL-2) regulatory action. Concanavalin A (Con A)-stimulated DNA synthesis in murine splenocytes was inhibited from 18.6 to 44.1% at sub-toxic concentrations of UDMH (10 to 50 μg/ml) and IL-2-dependent DNA synthesis in CTLL-20 cells was inhibited from 11.3 to 41.58% at subtoxic concentrations of UDMH (10 to 50 μg/ml). In addition, UDMH suppressed phorbol myristic acetate (PMA)-stimulated IL-2 production in EL-4 cells by up to 30% and slightly suppressed IL-2 production by Con A-stimulated murine splenocytes. In all cases, inhibition was evident at sub-toxic UDMH concentrations and was demonstrated to be independent of inactivation of IL-2 or interference with IL-2 absorption. It is suggested that UDMH has the potential to modify immune function through interference with IL-2 production and especially the lymphoproliferative response to IL-2.
Similar content being viewed by others
References
Abdou NI, Sagawa E, Hebert PJ (1976) Suppressor T cell abnormality in idiopathic systemic lupus erythematosus. Clin Immunol Immunopathol 6:192–199
Alcocer-Varela J, Alarcon-Segovia D (1982) Decreased production of and response to interleukin 2 by cultured lymphocytes from systemic lupus erythematosus. J Clin Invest 69:1388–1392
Altman A, Theofilopoulos AN, Weiner R, Katz DH, Dixon FJ (1981) Analysis of T cell function in autoimmune murine strains. Defects in production of, and responsiveness to, interleukin 2. J Exp Med 154:791–801
Back KC, Pinkerton MK, Cooper AB, Thomas AA (1963) Absorption, distribution, and excretion of 1,1-dimethylhydrazine (UDMH). Toxicol Appl Pharmacol 5:401–413
Baker PE, Gillis S, Smith KA (1979) Monoclonal cytolytic T cell lines. J Exp Med 149:273–283
Balazs T, Robinson CJG, Balter N (1981) Hydralazine-induced antinuclear antibodies in Beagle dogs. Toxicol Appl Pharmacol 57:452–456
Bresnihan B, Jasin JE (1977) Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus. J Clin Invest 59:106–116
Brown DM (1969) The reaction of hydrazine with pyrimidine bases. Meth Enzymol 12A:31–34
Budman DR, Merchant EB, Steinberg AD, Duft B, Gershwin ME, Lizzio E, Reeves JP (1977) Increased spontaneous activity of antibody forming cells in the peripheral blood of patients with active SLE. Arthritis Rheum 20:829
Buxman MM (1979) The role of enzymatic coupling of drugs to proteins in induction of drug-specific antibodies. J Inv Derm 73:250–255
Cannat A, Seligmann M (1976) Possible induction of antinuclear antibodies by isoniazid. Lancet i:185–187
Comens P (1956) Experimental hydralazine disease and its similarity to disseminated lupus erythematosus. J Lab Clin Med 471:444–454
Dauphinée MJ, Kipper SB, Wofsy D, Talal N (1981) Interleukin 2 deficiency is a common feature of autoimmune mice. J Immunol 127:2483–2487
Dubroff LM, Reid RJ Jr (1980) Hydralazine-pyrimidine interactions may explain hydralazine-induced lupus erythematosus. Science 208:404–406
Durant PJ, Harris RA (1980) Hydrazine and lupus. N Engl J Med 303:584–585
Dustan HP, Taylor RD, Corcoran AC, et al. (1954) Rheumatic and febrile syndrome during prolonged hydralazine therapy. J Amer Med Assoc 154:23–29
Farrar JJ, Mizel SB, Fuller-Farrar J, Farrar WL, Hilfiker ML (1980) Macrophage independent activation of helper T cells. I. Production of interleukin 2. J Immunol 125:793–799
Hahn BH, Sharp GC, Irvin WS, Kantor OS, Gardner CA, Bagby MK, Perry HM, Osterland CK (1972) Immune response to hydralazine and nuclear antigens in hydralazine-induced lupus erythematosus. Annals Internal Med 76:365–374
Heineman B (1971) Prophage induction in lysogenicEscherichia coli with simple hydroxylamine and hydrazine compounds. Appl Microbiol 21:726–731
Hothersall TE, Mowat AG, Duthie JJR, Alexander RRM (1968) Drug-induced lupus syndrome: A case report implicating isoniazid. Scott Med J 13:245–247
Kale SA (1985) Drug-induced systemic lupus erythematosus. Postgrad Med 77:231–242
Kimball RF (1977) The mutagenicity of hydrazine and some of its derivatives. Mutation Res 39:111–126
Kirkpatrick CH, Davis KC, Horsburgh CL (1985) Interleukin-2 production by persons with generalized lymphadenopathy syndrome or the acquired immune deficiency syndrome. J Clin Immunol 5:31–37
Krakauer RS, Walkman TA, Strober W (1976) Loss of suppressor T cells in adult NZB/NZW mice. J Exp Med 144:662–671
Lee SL, Chase PH (1975) Drug-induced systemic lupus erythematosus: A critical review. Semin Arthritis Rheum 5:83
Lorand L, Campbell LK, Robertson BJ (1972) Enzymatic coupling of isoniazid to proteins. Biochem 11:434–438
Mantovani G, Coiana A, Massidda A, Proto E, Floris C, Macció A, Pusciddu G, DelGiacco GS (1988) Role of interleukin-2 (IL-2) in cancer-related immune deficiency:In vitro response to IL-2, production of IL-2, and IL-2 receptor expression in patients with advanced cancer. Cancer Detect Prevent 12:149–159
Miyasaka N, Nakamura T, Russell IJ, Talal N (1984) Interleukin 2 deficiencies in rheumatoid arthritis and systemic lupus erythematosus. Clin Immunol Immunopath 31:109–117
Morgan DA, Ruscetti FW, Gallo RC (1976) Selectivein vitro growth of T lymphocytes from normal human bone marrows. Science 193:1007–1008
Murakawa Y, Takada S, Ueda Y, Suzuki N, Hoshino T, Sakanet (1985) Characterization of T lymphocyte subpopulations responsible for deficient interleukin 2 activity in patients with systemic lupus erythematosus. J Immunol 134:187–195
Orosz CG, Zinn NE, Olsen RG, Mathes LE (1985) Retrovirus mediated immunosuppression. I. FeLV-UV and specific FeLV proteins alter T-lymphocyte behavior by inducing hyporesponsiveness to lymphokines. J Immunol 134:3396–3403
Perry HM Jr (1973) Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. Am J Med 54:58–72
Prince HE, Kermani-Arab A, Fahey JL (1984) Depressed interleukin-2 receptor expression in acquired immune deficiency and lymphadenopathy syndromes. J Immunol 133:1313–1317
Reidenberg MM, Durant PJ, Harris RA, DeBoccardo G, Lahita R, Stenzel KH (1983) Lupus erythematosus-like disease due to hydrazine. Am J Med 75:365–370
Reynolds H, Caldwell JR (1957) Hydralazine syndrome-hypersensitivity or toxicity? J Amer Med Assoc 165:1823–1826
Roe FJC, Grant GA, Millican DM (1967) Carcinogenicity of hydrazine and 1,1-dimethylhydrazine for mouse lung. Nature (London) 216:375–376
Schiessel HW (1980) Hydrazine—Rocket fuel to synthetic tool. Aldrichimica Acta 13:33–40
Schmeltz J, Abidi S, Hoffman D (1977) Tumorigenic agents in unburned processed tobacco: N-nitrosodiethanolamine and 1,1-dimethylhydrazine. Cancer Ltrs 2:125–132
Schoen RT, Trentham D (1981) Drug-induced lupus: An adjuvant disease? Am J Med 71:5–8
Schopf RE, Hanauske-Abel HM, Tschank G, Schulte-Wisserman H, Gunzler V (1985) Effects of hydrazyl group containing drugs on leucocyte functions: An immunoregulatory model for the hydralazine-induced lupus-like syndrome. J Immunopharmacol 7:385–401
Schreier MH, Iscove NN, Tees R, Aarden L, Von Boehmer H (1980) Clones of killer and helper T cells: Growth requirements, specificity and retention of function in long-term culture. Immunol Res 51:315–336
Tarr MJ, McKown BJ, Olsen RG (1988a) Enhancement of murine mixed lymphocyte response by 1,1-dimethylhydrazine: Characterization and possible mechanism. Cancer Detect Prevent 12:573–581
Tarr MJ, Olsen RG, Bowen BL, Fertel RH (1988b)In vitro modulation of macrophage functions by 1,1-dimethylhydrazine (UDMH): Possible mechanism for UDMH induced immunoenhancement. Toxicology In Vitro 2:215–219
Tarr MJ, Olsen RG, Jacobs DL (1982)In vivo andin vitro effects of 1,1-dimethylhydrazine on selected immune functions. Immunopharmacology 4:139–147
Tosk J, Schmeltz I, Hoffman D (1979) Hydrazines as mutagens in a histidine requiring auxotroph ofSalmonella typhimurium. Mutation Res 66:247–252
Toth B (1973) 1,1-Dimethylhydrazine (unsymmetrical) carcinogens in mice. Light microscopic and ultrastructural studies on neoplastic blood vessels. J Natl Cancer Inst 50:181–194
Toth B, Wallcane L, Patil K, Schmeltz J, Hoffman D (1977) Induction of tumors in mice with the herbicide succinic acid 2,2-dimethylhydrazine. Cancer Ltrs 37:3497–3500
Umland SP, Smith SR, Strausser HR (1987) Production of and responsiveness to interleukin 2 in autoimmune BXSB mice. Cell Immunol 107:158–171
Welte K, Mertelsmann R (1985) Human interleukin 2: Biochemistry, physiology, and possible pathogenic role in immunodeficiency syndromes. Cancer Invest 3:34–49
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bauer, R.M., Tarr, M.J. & Olsen, R.G. Effect of 1,1-dimethylhydrazine on lymphoproliferation and interleukin 2 immunoregulatory function. Arch. Environ. Contam. Toxicol. 19, 148–153 (1990). https://doi.org/10.1007/BF01059824
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01059824