LIPOPOLYSACCHARIDE INDUCES SYNTHESIS OF MOUSE COLONY-STIMULATING FACTOR-I IN-VIVO

CSF-1 is a hemopoietic growth factor that regulates the survival, prol iferation, and differentiation of mononuclear phagocytes, cells that a re critical in the inflammatory response. In the case of Gram-negative infection, LPS plays an important role by inducing several cell types to produce the proinflammatory cytokines, IL-1, IL-6, and TNF-alpha. In this study, we examined the effects of i.p. administration of LPS o n CSF-1 expression in the mouse. Two- to sevenfold increases in the CS F-1 concentrations determined by RIA were evident within hours of LPS administration in serum, liver, kidney, lung, spleen, brain, intestine , and heart. While alterations in the CSF-1 receptor-mediated clearanc e of CSF-1 appeared not to account for the increased growth factor con centrations in LPS-treated animals, there was an early LPS-induced red uction of splenic [I-125]CSF-1 uptake consistent with tissue-specific down-modulation of CSF-1 receptors. The results of Northern analysis r evealed increased expression of a CSF-1 mRNA species in liver, lung, k idney, spleen, intestine, and heart following LPS treatment, demonstra ting that increased synthesis was responsible for the increased tissue CSF-1 concentrations. The increased expression and synthesis of CSF-1 in response to LPS may be essential for mobilizing and activating mon onuclear phagocytes in the inflammatory response.