| Abstract: |
We here investigated IL-1 modulation of cytokine receptors on murine bone marrow cells (BMC). In vivo, IL-1 treatment reduced >88% of granulocyte-CSF, >35% of TNF, and >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 >30% after 30 min, dramatically increased >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. |
| Keywords: |
controlled study; nonhuman; animal cell; mouse; animal; mice; cells, cultured; bone marrow; interleukin 1beta; animal experiment; dexamethasone; mice, inbred balb c; receptors, interleukin-1; dactinomycin; immunomodulation; bone marrow cell; ketoconazole; intravenous drug administration; receptors, immunologic; interleukin-1; mice, inbred c3h; cycloheximide; cell receptor; receptors, granulocyte colony-stimulating factor; receptor, macrophage colony-stimulating factor; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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