Effects of exogenous cytokines on intravascular clearance of bacteria in normal and splenectomized mice

Background: Pretreatment with interleukin-1 (IL-1), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) can improve alveolar macrophage bactericidal activity against pneumococci, These effects vary in eusplenic and asplenic mice. Likewise, these cytokines have been shown to improve survival after an aerosol pneumococcal challenge. Mice dying in these studies had positive blood cultures and disseminated infection, The purpose of this study was to determine the effect of cytokine pretreatment on intravascular clearance of bacteria from eusplenic and asplenic mice. Methods: Two weeks after splenectomy or sham operation, mice mere pretreated for various times with IL-I, G-CSF, or GM-CSF or their corresponding vehicles. Mice then received tail-vein injections of bacteria (0.1 mt), and quantitative blood cultures were performed 15 and 30 minutes thereafter. Results: Splenectomized mice had impaired clearance of both pneumococci and Pseudomonas compared with sham-operated mice (p < 0.05), IL-1 enhanced clearance in splenectomized mice (p < 0.001) but not in sham-operated mice (p not significant). G-CSF enhanced bacterial clearance in sham-operated mice (p < 0.01) but not in splenectomized mice (p not significant), GM-CSF enhanced clearance in both groups (p < 0.001). Conclusion: The net effects of exogenous cytokine therapy for infections depends on the state of the host defenses at the time of therapy. These agents may be useful as adjuvants for the treatment of infections, but further study is warranted.