Role of α1-proteinase inhibitor in restraining peritoneal inflammation in CAPD patients

Abstract

The concentration and functional state of α1-proteinase inhibitor (α1-PI) may modulate the expression of peritoneal phlogosis by affecting the activity of proteases and synthesis of autacoids. α1-PI is detectable in peritoneal effluents of peritonitis-free patients. α1-PI purified from peritoneal fluid of these patients was biologically active both in terms of inhibition of elastase activity and of synthesis of platelet activating factor (PAF). The biological activity of α1-PI could therefore explain the absence of detectable amounts of PAF in peritonitis free patients despite the presence of intraperitoneal concentrations of tumor necrosis factor-α (TNFα) that would be sufficient per se to induce the synthesis of PAF. In patients with acute infectious peritonitis, the concentration of immunoreactive α1-PI was significantly increased in respect to stable patients. However, α1-PI purified from patients with acute peritonitis was functionally inactive both on proteolytic activity on elastase and on TNFα-induced PAF synthesis by purified human PMN. The loss of α1-PI activity correlated with the number of peritoneal leukocytes and was probably dependent on oxidative inactivation. Indeed, treatment with reducing agent restored the inhibitory function of α1-PI. The inactivation of α1-PI in patients with peritonitis was associated with the presence of PAF in peritoneal dialysates. These results suggest that α1-PI prevents the proteolytic action and cell activation leading to PAF synthesis in peritonitis free patients. However, inactivation of its function by oxidants generated during the inflammatory process may lead to proteolytic injury and unrestrained synthesis of inflammatory mediators during peritonitis.