Effects of interleukin-1 (IL-1) on postsurgical macrophage secretion of protease and protease inhibitor activities

Although peritoneal macrophages secrete a variety of inflammatory mediators and proteases during postsurgical repair of the peritoneum, regulation of this secretion is poorly understood. Here, the responsivity of peritoneal macrophages to interleukin-1 (IL-1) stimulation in vitro, measured by the secretion of protease and protease inhibitor activities, was evaluated as a function of postsurgical time. Macrophages were harvested at various times after peritoneal sidewall abrasion, isolated by discontinuous density centrifugation and cultured with varying concentrations of IL-1. IL-1 increased the secretion of plasminogen activator (PA) activity by peritoneal macrophages in a concentrationdependent manner on postsurgical Days 0, 3, 10, and 14. Macrophages harvested on postsurgical Day 1 after surgery responded only to high concentration of IL-1, while on Days 5 and 7 all doses of IL-1 stimulate PA. On Days 7, 10, and 14 after surgery, the secretion of PA activity (after acid treatment) by postsurgical macrophages was generally high and increased with IL-1 treatment. The level of PA activity after inactivation of acid labile inhibitors (PAI) also increased in a dose-dependent manner on Days 0, 3, and 5. Although Day 1 macrophages expressed the highest PAI activity of all groups, they had relatively low responsivity to IL-1 with regards to PAI secretion. The level of elastase activity by postsurgical macrophages was lowest on Day 1, highest on Day 7, and decreased thereafter. All concentrations of IL-1 inhibited elastase activity of macrophages on Day 7. Collagenase activity in acid-treated media increased with increasing doses of IL-1 on Days 3 and 7. In conclusion (1) IL-1 stimulated secretion of both PA and PAI by postsurgical macrophages, (2) the secretion of PA activity by unstimulated peritoneal macrophages was highest on Days 5 and 7 and also showed the greatest relative responsivity to exogenous IL-1 at these time points, (3) the secretion of PAI activity did not appear to reach a maximum plateau even with 100 U IL-1; however, PAI production was reduced after Day 10, (4) macrophages from postsurgical Day 1 were less responsive to IL-1 in both PA and PAI production, and (5) IL-1 decreased elastase activity in a concentrationdependent manner.