Inhibition of experimental allergic encephalomyelitis by lithium chloride: specific effect or nonspecific stress?

Intraperitoneal injections of lithium chloride inhibited development of experimental allergic encephalomyelitis (EAE) in rats. The degree of inhibition was inversely related to the intensity of the immunologic stimulation, which depended on the choice of adjuvant. High dosage of lithium, the intraperitoneal route, and an intermittent schedule of administration were required to achieve suppression of EAE. This suggested that the immunosuppression was a toxic effect, mediated, at least in part, through the hypothalamic-pituitary-adrenal cortex axis. This hypothesis was supported by evidence that the lithium treatment schedule, especially the intermittent schedule, had caused adrenal cortical activation with thymolysis in intact rats and that it was lethal to adrenalectomized rats. Lithium also inhibited EAE produced by adoptive immunization, thus implicating the efferent arm of the immune response. A single dose of lithium was effective in this form of EAE, even in adrenalectomized rats. Therefore lithium affects EAE by both specific immunosuppressive and nonspecific adrenocortical-dependent mechanisms.