The Effect of Lithium Upon Granulocyte Production in vitro and in vivo in the Mouse
Following the institution of lithium therapy in the management of manic states, observers noted that leukocytosis and neutrophilia frequently occurred (Risetto and Gassano, 1952; Mayfield and Brown, 1966; O’Connell, 1970; Murphy and Goodwin, 1971; Shopsin and Friedman, 1971). In 1973, Tisman et al. postulated that the neutrophilia was due to an increase in the total blood granulocyte pool and also demonstrated augmentation of granulocyte proliferation in vitro (Tisman et al., 1973). In 1975, it was demonstrated that lithium enhanced colony stimulating activity (CSA) production in mice (Harker et al., 1975), and humans (Joyce and Chervenick, 1975), suggesting that this CSA alteration had a mechanistic role in vivo. In the present study, we have examined the action of lithium upon murine granulocytopoiesis in vivo and in vitro in order to: 1) further define the action of lithium upon CSA production by lung, adherent peritoneal cells, and marrow; 2) to examine the direct effect of lithium upon the proliferation of colony forming cells (CFC) or their progeny; and 3) to test the hypothesis that lithium stimulation of CSA production is due to modulation of cellular cyclic AMP (cAMP) levels.
KeywordsPeritoneal Cell Nephrogenic Diabetes Insipidus Colony Form Cell Howard Hughes Medical Institute Colony Stimulate Activity
Unable to display preview. Download preview PDF.
- Chervenick, P.A., Boggs, D.R., Marsh, J.C., Cartwright, G.E. and Wintrobe, M.M., 1973, Quantitative studies of blood and bone marrow neutrophils in normal mice, Amer. Jour. Phys. 215:353.Google Scholar
- Fehir, K.M. and Rossof, A.H., 1977, Lithium carbonate stimulation of marrow colony forming units and peripheral granulocytes in a canine model, Blood 50:145 (Supplement 1).Google Scholar
- Hammond, W.P. and Dale, D.C., 1979, Canine cyclic hematopoiesis: Treatment with lithium, Clin. Res. 27:461A.Google Scholar
- Harker, G.W., Rothstein, G., Clarkson, D.W. and Athens, J.W., 1975, Stimulation of neutrophil production by lithium, Clin. Res. 23:103A.Google Scholar
- Iscove, N.N., 1972, Technique for culture of human CFU-c, in “In vitro culture of hemopoietic cells,” (Van Bekkum, D.W. and Dicke, K.A., eds.), Rijswijk Radiobiol. Inst. TNO.Google Scholar
- Joyce, R.A. and Chervenick, P.A., 1975, Effect of lihtium on the release of colony-stimulating activity (CSA) from blood leukocytes, Proc. Amer. Soc. Hematol. 18:126.Google Scholar
- Joyce, R.A. and Chervenick, P.A., 1979, Lithium effect on granulopoiesis following vinblastine, Clin. Res. 27:388A.Google Scholar
- Murphy, D.L. and Goodwin, F.K., 1971, Leukocytosis during lithium treatment, J. Psych. Res. 127:1559.Google Scholar
- O’Connell, R.A., 1970, Leukocytosis during lithium carbonate treatment, Int. J. Pharmacopsychiatry 4:30.Google Scholar
- Risetto, G. and Gassano, G., 1952, Variazioni del sanque perifico nella intossicazione sperimentale da sali di litio, Riv. Patol. Clin. Sper. 7:202.Google Scholar
- Sheridan, J.W. and Metcalf, D., 1974, CSF production and release following endotoxin, in “Hemopoiesis in Culture, 2nd International Workshop,” (Robinson, W.A., ed.), Washington, D.C., NIH 74-205.Google Scholar