Cysteamine produces dose-related bidirectional immunomodulatory effects in mice

HU Bryant, JW Holaday and EW Bernton

Department of Medical Neuroscience, Walter Reed Army Institute of Research, Washington, DC.

The sulfhydryl reducing agent, cysteamine, is known to functionally inactive prolactin and other neurohormones that have been recently shown to play a role as immunomodulators. Cysteamine was administered to mice to evaluate its effects upon immune organ size and mitogen- induced lymphocyte proliferative responses in relation to corresponding effects on the immunomodulatory hormones, prolactin and corticosterone. The lowest dose of cysteamine, 12.5 mg/kg given once per day for 3 consecutive days, produced significant elevations of both concanavalin A-(Con A) and lipopolysaccharide-induced blastogenesis. Serum prolactin levels were also significantly elevated with 12.5 mg/kg cysteamine. By contrast, at 300 and 400 mg/kg, cysteamine significantly reduced Con A and lipopolysaccharide-induced proliferation. This suppression of mitogen-induced proliferative responses was accompanied by marked atrophy of the thymus. Levels of both prolactin and corticosterone in the serum were significantly reduced at 400 mg/kg cysteamine. A positive correlation was observed between serum prolactin levels and Con A-induced proliferation as well as between serum prolactin and corticosterone levels in cysteamine-treated mice. The immunomodulatory effects of cysteamine were not limited to correlative effects on neuroendocrine parameters. A similar pattern of effects was observed following in vitro administration of cysteamine. Low concentrations in vitro (0.1 mM) stimulated Con A-induced proliferation of normal mouse splenocytes, and higher concentrations in vitro (2.0 mM) suppressed proliferation. These studies indicate that, depending upon the dose, cysteamine has bidirectional effects on mitogen-induced proliferation of lymphocytes; these effects are correlated with cysteamine-related alterations in the neuroendocrine status of the animal but may also be observed with direct addition of the drug to stimulated lymphocytes in culture.

Volume 249, Issue 2, pp. 424-429, 05/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				S E Walker Bromocriptine treatment of systemic lupus erythematosus Lupus, October 1, 2001; 10(10): 762 - 768. [Abstract] [PDF]

				S Suwannaroj, A Lagoo, D Keisler, and R W McMurray Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE) Lupus, April 1, 2001; 10(4): 258 - 265. [Abstract] [PDF]

				S E Walker Treatment of systemic lupus erythematosus with bromocriptine Lupus, March 1, 2001; 10(3): 197 - 202. [Abstract] [PDF]

				S E Walker, D Miller, D L Hill, and G R Komatireddy Prolactin, a pituitary hormone that modifies immune responses: Proceedings of the Mini-symposium on Prolactin and SLE, held at the 5th International Conference on Systemic Lupus Erythematosus, Cancun, Mexico Lupus, July 1, 1998; 7(6): 371 - 375. [PDF]