We here investigated IL-1 modulation of cytokine receptors on murine bone marrow cells (BMC). In vivo, IL-1 treatment reduced greater than 88% of granulocyte-CSF, greater than 35% of TNF, and greater than 51% of granulocyte/macrophage-CSF binding to BMC after 3 h, and returned to base line after 48 h. However, IL-1 binding to BMC decreased greater than 30% after 30 min, dramatically increased greater than 9-fold between 6 and 10 h, and declined to base line after 48 h. In vitro incubation of BMC with IL-1 did not markedly alter IL-1 and granulocyte-CSF binding, suggesting that modulation of granulocyte-CSF and IL-1 binding to BMC by IL-1 in vivo is due to an indirect mechanism. Further in vitro studies showed that IL-1 binding to BMC was specifically induced by glucocorticoids rather than other steroids, and is a time- and dose-dependent process. IL-1 induced IL-1R up-regulation was suppressed by ketoconazole, cycloheximide, and actinomycin D in a dose-dependent manner. In addition, in vivo dexamethasone imitated the action of IL-1 in stimulating IL-1 binding to BMC and in inducing neutrophilia. Furthermore, IL-1 binding to BMC from sham mice 8 h after IL-1 administration was 2.5 times higher than that observed in adrenalectomized mice. Our results demonstrate, for the first time, that in vivo IL-1-induced increased IL-1 binding to BMC was due to an indirect mechanism, and glucocorticoids stimulated IL-1 binding to BMC in vivo and in vitro. Inasmuch as serum glucocorticoid levels can be elevated by IL-1 in vivo, these results reveal a novel mechanism by which IL-1 modulates its own receptors in vivo.

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