EFFECT OF LITHIUM IN IMMUNODEFICIENCY - IMPROVED BLOOD-CELL FORMATIONIN MICE WITH DECREASED HEMATOPOIESIS AS THE RESULT OF LP-BM5 MULV INFECTION

Lithium salts have been demonstrated to induce the production of hemat opoietic cells following administration in vivo and to minimize the re duction of these cells following treatment with either radiation, chem otherapeutic or antiviral drugs. We have previously demonstrated that lithium, when administered in vivo to immunodeficient mice infected wi th LP-BM5 MuLV (MAIDS) significantly reduced the development of lympha denopathy, splenomegaly, and the lymphoma associated with late-stage i mmunodeficiency disease in this model, and increased the survival of t hese animals compared to virus-infected controls not receiving lithium . We report here the results of in vivo studies in the MAIDS model tha t determined the effect of lithium on peripheral blood indices and the number of myeloid (CFU-GM), erythroid (BFU-E) and megakaryocyte (CFU- Meg) hematopoietic progenitors from bone marrow and spleen harvested f rom immunodeficient mice receiving lithium carbonate (1 mM) placed in their drinking water compared to virus-infected controls not receiving lithium. Time-points evaluated were at weeks 1, 5, 9, 13, 17, and 21 postviral infection. Virus-control mice not receiving lithium demonstr ated all the signs that are characteristic of MAIDS, i.e., splenomegal y, lymphadenopathy, hypergammaglobulinemia, reduced hematopoiesis, and death. Infected mice receiving lithium demonstrated diminished presen ce of splenomegaly, lymphadenopathy, hypergammaglobulinemia, no suppre ssion of hematopoiesis nor mortality. Enhanced hematopoiesis was demon strated by neutrophilia, lymphocytosis, thrombocytosis, and erythrocyt osis that was evident by increased myeloid, erythroid, and megakaryocy te progenitor cells cultured from bone marrow and spleen. These studie s further demonstrate that lithium influences the disease process in t he MAIDS model and restricts the development of hematopoietic suppress ion that develops in this retroviral animal model of immunodeficiency.