Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis

Am J Kidney Dis. 2000 Apr;35(4):644-52. doi: 10.1016/s0272-6386(00)70011-4.

Abstract

Continuous ambulatory peritoneal dialysis (CAPD) has emerged as an important dialysis treatment modality worldwide. One of the major complications is bacterial peritonitis, which may result in subsequent technique failure because of loss of peritoneal clearance or peritoneal fibrosis. Bacterial peritonitis leads to the release of proinflammatory cytokines from resident and infiltrating cells in the peritoneal cavity. We studied 35 patients undergoing CAPD with acute bacterial peritonitis. All patients treated with antibiotics for 2 weeks after the clinical diagnosis of peritonitis had a good recovery. Peritoneal dialysate effluent (PDE) was collected on days 1, 3, 5, 10, 21, and 42 after the start of treatment. Cell populations were monitored by flow cytometry. PDE levels of interleukin-1beta (IL-1), IL-6, transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (FGF) were measured by enzyme-linked immunosorbent assay. Gene transcription of TGF-beta in macrophages from PDE was measured by quantitative polymerase chain reaction. Bacterial peritonitis was associated with a sharp increase in total cell and neutrophil counts (400-fold) in PDE up to 3 weeks after peritonitis despite clinical remission (P < 0.0001). There was an increased absolute number of macrophages during the first 3 weeks despite the reduced percentage of macrophages among total cells in PDE compared with noninfective PDE. There was a progressive increase in the percentage of mesothelial cells or dead cells in the total cell population in PDE over the entire 6-week period. PDE levels of IL-1, IL-6, TGF-beta, and FGF increased markedly on day 1 before their levels decreased gradually. PDE levels of these cytokines or growth factors were significantly greater than those in noninfective PDE (n = 76) throughout the study period (P < 0.01). Similarly, TGF-beta complementary DNA (cDNA) molecules per macrophage were significantly greater than those of macrophages in noninfective PDE throughout this period (P < 0.01). There was no significant correlation between PDE levels of TGF-beta and TGF-beta cDNA molecules per macrophage, suggesting that peritoneal macrophages are not the only source of TGF-beta in PDE. We conclude there is an active release of proinflammatory cytokines and sclerogenic growth factors through at least 6 weeks despite apparent clinical remission of peritonitis. The peritoneal cytokine networks after peritonitis may potentially affect the physiological properties of the peritoneal membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Infections / etiology
  • Bacterial Infections / metabolism*
  • Cytokines / analysis*
  • DNA, Complementary / analysis
  • Female
  • Fibroblast Growth Factor 2 / analysis
  • Fibrosis / etiology
  • Fibrosis / metabolism
  • Flow Cytometry
  • Humans
  • Interleukin-1 / analysis
  • Interleukin-6 / analysis
  • Macrophages, Peritoneal / chemistry
  • Male
  • Middle Aged
  • Peritoneal Dialysis, Continuous Ambulatory / adverse effects*
  • Peritoneal Diseases / etiology
  • Peritoneal Diseases / metabolism
  • Peritonitis / etiology
  • Peritonitis / metabolism*
  • Polymerase Chain Reaction
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / genetics

Substances

  • Cytokines
  • DNA, Complementary
  • Interleukin-1
  • Interleukin-6
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2