Cysteamine produces dose-related bidirectional immunomodulatory effects in mice.
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.
Bryant
H U
HU
Department of Medical Neuroscience, Walter Reed Army Institute of Research, Washington, DC.
Holaday
J W
JW
Bernton
E W
EW
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003543:Cysteamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007107:Immune System / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011388:Prolactin / Q000097:blood
D008070:Lipopolysaccharides; D003208:Concanavalin A; D003543:Cysteamine; D011388:Prolactin; D003345:Corticosterone