Induction of prolonged elevation of interleukin 2 in the culture medium of murine splenocytes by their precultivation before mitogenic stimulations and its potentiation by glucocorticoid treatment and restraint stress loading.

Enhancement of interleukin 2 (IL 2) activity in the culture medium of splenocytes of BALB/c mice occurred if the cells were precultured before concanavalin A (Con A) and phytohemagglutinin stimulation. This enhancing effect was much greater in autoimmune NZB/W F1 mice than BALB/c mice, the induced high level of IL 2 being sustained for 11 days of culture. The continuously elevated IL 2 activity induced by precultivation was lowered by the addition of the intact normal thymocytes, but not by precultured or irradiated thymocytes. Lipopolysaccharide-induced anti-DNA antibody production in the precultured splenocytes of NZB/W F1 mice was higher than that in freshly prepared ones. Mitogen-induced proliferative responses in both freshly prepared thymocytes and splenocytes of BALB/c mice treated with hydrocortisone (HC) were significantly enhanced, although the number of splenocytes and the primary in vitro plaque-forming cell response to sheep erythrocytes were reduced. Con A-induced IL 2 elevation in the supernatant of splenocytes precultured before the antigen stimulation was potentiated in HC-treated mice. Similar results were obtained in splenocytes from BALB/c mice loaded with restraint stress. These findings suggest that disturbance of IL 2 metabolism might be involved in the pathogenesis of NZB/W F1 mice, and an increased level of glucocorticoids might lead to a condition in which the body becomes susceptible to the development of hyper-immune responses.