Restoration of hematopoietic activity by lipid A analogue GLA-60 in cyclophosphamide-treated immunosuppressed mice.

Administration of GLA-60, a synthetic lipid A-subunit analogue, significantly increased the numbers of macrophages, lymphocytes and polymorphonuclear leukocytes (PMN) in the peritoneal cavity of cyclophosphamide (CY)-treated immunosuppressed mice. Colony-stimulating factors (CSFs) were induced by GLA-60 in sera of both normal and CY-treated mice in a dose-dependent manner. The CSFs induced in mouse sera stimulated growth of bone marrow stem cells (BMC) which derived from either CY-treated or untreated mice in CSF assay. Three different colonies were formed in CSF assay consisting of granulocytes (G), macrophages (M) and mixed population. Addition of serum CSFs as well as exogenous addition of interleukin 3 (IL-3) or G-CSF to BMC taken from mice 1 day after CY-treatment induced high activity to stimulate the proliferation of those cells. Production of interleukin 1 (IL-1) was also stimulated in sera of CY-treated and untreated mice by administration of GLA-60. These results indicate that restoration of hematopoietic activity by GLA-60 in CY-immunosuppressed mice is due to induction of CSFs and IL-1, which synergistically act on proliferation and differentiation of pluripotential stem cells in bone marrow.