Metabolism of 25-OH-vitamin D₃ by peritoneal macrophages from CAPD patients

The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)₂D₃), is produced mainly by the kidney, but there is evidence for extrarenal production in certain circumstances. We studied whether peritoneal macrophages (PM) from CAPD patients were capable of metabolizing 25-OH-D₃ to 1,25(OH)₂D³. We found that PM were able to metabolize 25-OH-D₃ in vitro; the main product following 16 hours of incubation was 19-nor, 10-oxo, 25-OH-D₃ with smaller amounts of 1,25(OH)₂D₃. However, after shorter incubations of three and five hours a larger portion of 1,25(OH)₂D₃ was produced. The metabolism of 25-OH-D³ was greatly enhanced in PM harvested during episodes of peritonitis. This property was specific for PM of CAPD patients, and was not found in PM from normal subjects. However, incubation of control PM with peritoneal effluent from CAPD patients resulted in induction of the ability of these cells to metabolize 25-OH-D₃. This induction was enhanced by preincubation with peritoneal effluent from CAPD patients suffering from peritonitis. Prostaglandin E₂ was found to be involved in this synthesis: addition of PGE₂ to normal PM induced metabolism of 25-OH-D₃, and incubation of PM from CAPD patients with indomethacin decreased the metabolism of 25-OH-D₃. The vitamin D metabolites produced by PM from CAPD patients could have a role in immunological resistance to peritoneal infections.