Modulation of circulating colony-stimulating activity in mice: combined effects of IL-1 and bacterial or indomethacin treatment.

We have investigated the effects of interleukin 1 (IL-1) administration on circulating levels of colony-stimulating activity (CSA) in intact or neutropenic mice. Intact or cyclophosphamide-treated mice received human rIL-1 beta according to different regimens, and their sera were assayed for CSA at 4, 24 or 48 h. The results indicated that (1) cyclophosphamide alone significantly increased the level of circulating CSA, (2) administration of IL-1 to intact or neutropenic mice resulted in a biphasic pattern of CSA response, an early burst at 4 h being followed at 24-48 h by a significant decrease. In nongranulocytopenic mice, the combined treatment with IL-1 and bacterial cells also resulted in a biphasic pattern of CSA response. However, when IL-1 was administered in concurrence with the cyclo-oxygenase inhibitor indomethacin, sustained CSA levels could be observed for a prolonged period of time. These data expand upon our previous observations on modulation of CSA by IL-1 in granulocytopenic mice, and further support the concept that IL-1 may have both positive and negative effects on the expression of circulating CSA.