Modulation of colony-stimulating activity by interleukin 1 mice: opposing effects of combined treatment with indomethacin of prostaglandin E₂

Following previous observations that interleukin 1 (IL-1) may have both positive and negative effects on the levels of circulating colony-stimulating factors (CSF) in mice, we have investigated the impact of human rIL-1β administration on serum concentrations of colony-stimulating activity (CSA, as defined by biossay) and macrophage-specific colony-stimulating factor (CSF-1, measured by RIA). In addition, we have studied the effects of IL-1 administered in conjunction with indomethacin or prostaglandin (PG) E₂. Besides confirming the finding that exogenous IL-1 leads to a rapid increase in CSF detection, we obtained evidence that IL-1 may also result in the production of cyclo-oxygenase products that down-regulate the IL-1-induced burst in CSA and CSF-1 levels. While co-treatment of mice with indomethacin led to a further increase in CSF detection, the combined exposure to IL-1 and PGE₂ rsulted in a significant impairment of the stimulatory activity of IL-1.