In vivo and in vitro Effects of Lithium on Granulopoiesis in Human Neutropenic Disorders

  • William A. Robinson
  • Maureen A. Entringer
  • James Huber
  • Ramesh Gupta
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 127)


Administration of lithium salts to humans increases peripheral blood neutrophil counts (O’Connell, 1970; Shopsin et al., 1971). It has been shown that this is due to a true increase in neutrophil mass, rather than a shift in peripheral blood neutrophil pools (Tisman et al., 1973; Rothstein et al., 1978). The mechanism of action of lithium in this regard has been studied by a number of investigators using in vitro techniques (Joyce and Chervenick, 1975; Harker et al., 1977; Morley and Galbraith, 1978; Spitzer et al., in press). It has been shown that lithium leads to increased production of the granulocyte colony stimulating factor (CSF) by adherent peripheral blood and bone marrow cells. CSF is the presumed humoral regulator of granulocyte production and has been partially characterized as a glycoprotein with a molecular weight of approximately 35,000 daltons (Robinson and Mangalik, 1975; Metcalf, 1977). Further, it has been shown that lithium does not alter the functional capacity of neutrophils, suggesting that it may be useful as a therapeutic agent in human neutropenic disorders (Rossof and Coltman, Jr., 1976; Cohen et al., 1979).


Bone Marrow Cell Colony Formation Feeder Layer Lithium Chloride Lithium Salt 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Barrett, A.J., Hugh-Jones, K., Newton, K., and Watson, J.G., 1977, Lithium therapy in aplastic anemia, The Lancet 1:202.CrossRefGoogle Scholar
  2. Catane, R., Kaufman, J., Mittelman, A., and Murphy, G.P., 1977, Attenuation of myelosuppression with lithium, N. Engl. J. Med. 297:452.PubMedCrossRefGoogle Scholar
  3. Charron, D., Barrett, A.J., Faille, A., Alby, N., Schmidt, T., and Degos, L., 1977, Lithium in acute myeloid leukemia, The Lancet 1:1307.CrossRefGoogle Scholar
  4. Cohen, M.S., Zakhireh, B., Metcalf, J.A., and Root, R.K., 1979, Granulocyte function during lithium therapy, Blood 53:913.PubMedGoogle Scholar
  5. Gupta, R., Robinson, W.A., and Albrecht, D., 1975, Granulpoietic activity in Felty’s syndrome, Ann. Rheum. Dis. 34:156.PubMedCrossRefGoogle Scholar
  6. Gupta, R.C., Robinson, W.A., and Smyth, C.J., 1975, Efficacy of lithium in rheumatoid arthritis with granulocytopenia (Felty’s syndrome), Arth. Rheum. 18:179.CrossRefGoogle Scholar
  7. Gupta, R.C., Robinson, W.A., and Kurnick, J.E., 1976, Felty’s syndrome, Am. J. Med. 61:29.PubMedCrossRefGoogle Scholar
  8. Harker, W.G., Rothstein, G., Clarkson, D.W., Athens, J.W., and Macfarlane, J.L., 1977, Enhancement of colony-stimulating activity production by lithium, Blood 49:263.PubMedGoogle Scholar
  9. Joyce, R.A. and Chervenick, P.A., 1975, Effect of lithium on the release of colony stimulating activity (CSA) from blood leukocytes, Proc. Am. Soc. Haematol. 18:126.Google Scholar
  10. Metcalf, D., 1977, “Hemopoietic Colonies,” Springer-Verlag, Berlin, Heidelberg, New York.CrossRefGoogle Scholar
  11. Morley, Jr., D.C. and Galbraith, P.R., 1978, Effect of lithium on granulo-poiesis in culture, Can. Med. Assoc. J. 118:288.PubMedGoogle Scholar
  12. O’Connell, R.A., 1970, Leukocytosis during lithium carbonate treatment, Int. J. Pharmacopsychiatry 4:30.Google Scholar
  13. Pike, B.L. and Robinson, W.A., 1970, Human bone marrow colony growth in agar-gel, J. Cell. Physiol. 76:77.PubMedCrossRefGoogle Scholar
  14. Robinson, W.A. and Pike, B.L., 1970, Leukopoietic activity in human urine. The granulocytic leukemias, N. Engl. J. Med. 282:1291.PubMedCrossRefGoogle Scholar
  15. Robinson, W.A., Entringer, M.A., and Otsuka, A.L., 1972, In vitro studies in acute granulocytic leukaemia in humans, in “The Nature of Leukaemia” (P.C. Vincent, ed.), pp. 151–161, V.C.N. Blight, Sydney, N.S.W., Australia.Google Scholar
  16. Robinson, W.A. and Mangalik, A., 1975, The kinetics and regulation of granulopoiesis, Semin. Hematol. 12:7.PubMedGoogle Scholar
  17. Rossof, A.H. and Coltman,Jr., C.A., 1976, The effect of lithium carbonate on the granulocyte phagocytic index, Experientia 32:238.PubMedCrossRefGoogle Scholar
  18. Rothstein, G., Clarkson, D.R., Larsen, W., Grosser, B.I., and Athens, J.W., 1978, Effect of lithium on neutrophil mass and production, N. Engl. J. Med. 298:178.PubMedCrossRefGoogle Scholar
  19. Shopsin, S., Friedman, R., and Gershon, S., 1971, Lithium and leukocytosis, Clin. Pharmacol. Ther. 12:923.PubMedGoogle Scholar
  20. Spitzer, G., Verma, D.S., Barlogie, B., McCredie, K.G., and Dicke, K., 1979, Possible mechanisms of action involved in the augmentatioin of in vitro spontaneous myeloid colony formation by lithium, Cancer Res., in press.Google Scholar
  21. Stein, R.S., Beaman, C., Ali, M.Y., Hansen, R., Jenkins, D.D., and Jume’an, H.G., 1977, Lithium carbonate attenuation of chemotherapy-induced neu-tropenia, N. Engl. J. Med. 297:430.PubMedCrossRefGoogle Scholar
  22. Tisman, G., Herbert, V., and Rosenblatt, S., 1973, Evidence that lithium induces human granulocyte proliferation: Elevated serum vitamin B12 binding capacity in vivo and granulocyte colony proliferation in vitro, Br. J. Haematol. 24:767.PubMedCrossRefGoogle Scholar
  23. Tisman, G., 1974, Lithium carbonate protection against drug-induced leukopenia in lymphosarcoma patients, IRCS 2:1509.Google Scholar
  24. Van Zant, G and Goldwasser, E., 1979, Competition between erythropoietin and colony-stimulating factor for target cells in mouse marrow, Blood 53:946.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • William A. Robinson
    • 1
  • Maureen A. Entringer
    • 1
  • James Huber
    • 1
  • Ramesh Gupta
    • 1
  1. 1.Divisions of Medical Oncology and Rheumatic Diseases Department of MedicineUniversity of Colorado Medical CenterDenverUSA

Personalised recommendations