CAPD peritonitis induces the production of a novel peptide, daintain/allograft inflammatory factor-1

Abstract

Objectives: To study the occurrence of a novel macrophage-derived peptide, daintain/allograft inflammatory factor-1 (AIF-1), in dialysate from continuous ambulatory peritoneal dialysis (CAPD) patients at commencement and after a follow-up period of therapy and during peritonitis. In addition, we studied peptide production in response to bacterial stimulation of monocytes and macrophages. Design: Peritoneal fluid and supernatants from cells stimulated with different bacteria were analyzed for daintain/AIF-1. Patients and Setting: Peritoneal fluid was obtained from 5 patients at commencement of CAPD therapy and during 8 weeks' follow-up, and from 14 patients (10 males, 4 females) during CAPD peritonitis and during the noninfected steady state. All patients were admitted to the Karolinska Hospital. A human monocyte cell-line, THP-1 was differentiated to macrophages, and both monocytes and macrophages were stimulated with live and heat-inactivated Escherichia coli, Staphylococcus aureus, and S. epidermidis. Cells were also stimulated with interleukin (IL)-1β and interferon gamma (IFNγ). Daintain/AIF-1 was analyzed with radioimmunoassay technique and IL-8 with enzyme immunoassay technique. Results: An increased production of daintain/AIF-1 was observed in the first spent dialysate in the newly started CAPD patients, with a decrease during the follow-up period (p < 0.05). During peritonitis, the first spent dialysate revealed significantly higher levels of daintain/AIF-1 (3.9 ng/mL) compared to the noninfected state (0.8 ng/mL), with production normalizing after 9 - 12 days. Bacterial stimulation with E. coli, S. aureus, or S. epidermidis induced higher daintain/AIF-1 response in monocytes compared to macrophages; (p < 0.05). Live bacteria induced higher production of the peptide compared to heat-inactivated bacteria (p < 0.05). Interleukin-1β and IFNγ were used to stimulate monocytes and macrophages; however, no daintain/AIF-1 production was found, although increased IL-8 levels were detected. Conclusion: CAPD peritonitis induces a high and prominent daintain/AIF-1 response. Bacteria are able to induce a response of the peptide from monocytes and macrophages, and it is likely that the virulent parts of the bacteria are heat-labile structures. The early rise in daintain/AIF-1 might be used as a marker of CAPD peritonitis.