Specificity of lithium (Li+) to enhance the production of colony stimulating factor (GM-CSF) from mitogen-stimulated lymphocytes in vitro.

We report here studies demonstrating the ability of Li+ to increase GM-CSF production from both mitogen-induced spleen and thymus cells prepared as serum-free conditioned media (SF-SCCM, SF-TCCM). GM-CSF activity was both a mitogen and Li+ specific mediated event (P less than 0.001-0.001). Identical cultures prepared with either Na, K, Ca, or Mg did not induce GM-CSF activity as compared to Li. No GM-CSF activity was observed in the absence of mitogen. Furthermore, indomethacin (10(-6) M), a potent inhibitor of prostaglandin (PG) synthesis, produced an even greater enhancement in GM-CSF than control cultures prepared without indomethacin. These data indicate Li may enhance GM-CSF production by inhibiting the ability of PG to decrease GM-CSF production. CFU-Mk colony formation was not significantly influenced by any specific cation-induced mitogen (CM), suggesting Li's ability to stimulate megakaryocytopoiesis may be mediated via a more direct stem cell effect. Furthermore, Li-derived (CM) significantly reduced both CFU-E and BFU-E, while those CMs prepared in the presence of K and Ca significantly increased erythroid colony formation. These effects could be mediated via alterations in the production of BPA. These studies demonstrate the unique capacity of cations to influence the differentiation of committed hematopoietic stem cells possibly by modulating the production of such factors required for hematopoietic differentiation.