The mechanism of lithium carbonate-induced augmentation of colony-stimulating activity elaboration in man

Lithium carbonate (Li) has been reported to elevate granulocyte counts in patients with certain neutropenic disorders and to improve chemotherapy-induced granulocytopenia. To investigate the mechanisms involved in the increase in myelopoiesis, the effect of Li on monocytemacrophage (M phi)- and T-lymphocyte (TL)-derived colony-stimulating activity (CSA) were studied in vitro. Li induced a dose-related increase in both M phi- and TL-derived CSA over that in non-Li-stimulated cell populations. However, the increase was significant (p less than 0.007) only at a higher concentration of Li (2 mEq/l). The results of co-incubating TL with M phi with or without Li indicated that Li significantly enhanced synergistic CSA production by the two cell populations (p less than 0.02). We further demonstrated the presence of a larger proportion of M phi with TL rosettes in the presence of Li (62%) than in its absence (21%). Further experiments with concanavalin A (Con-A)-inducible suppressor TL suggested that Li effectively blocks the suppressor TL-mediated suppression of CSA. These data suggest that Li enhances M phi and TL interaction which results in an augmented CSA elaboration. Further, Li would be more effective in those neutropenic disorders associated with enhanced suppressor TL activity. For an optimal effect, however, Li would require appropriately functioning M phi and non-suppressor subsets of TL and an intact stem cell pool.