Suppressor Resident Peritoneal Macrophages and Peritonitis Incidence in Continuous Ambulatory Peritoneal Dialysis

Abstract

Our study was designed to see if peritoneal macrophages (PM) of continuous ambulatory peritoneal dialysis (CAPD) uremic patients, by weaking local defense, could contribute to an increase of peritonitis incidence. Coincubation of nonadherent control responding cells (NACRC) and PM from normal subjects or CAPD patients with low peritonitis incidence (LPI) did not modify blastogenic response of cells to PHA. Coincubation of NACRC and PM from CAPD patients with high peritonitis incidence (HPI) produced noticeable decrease in blastogenic response; these PM, unable to produce normal amounts of Interleukin-1 (IL-1), released large amounts of prostaglandin E₂ (PGE₂). CAPD patients with LPI and normal subjects produced both substances in similar amounts. PM of CAPD patients with HPI were less able to kill bacteria than those from normal subjects and CAPD patients with LPI, showing a stronger suppressor effect on local defense. This suppressor activity correlated directly to PGE₂ release and inversely to IL-1 production. We can hypothesize that in some uremic patients, subpopulations of macrophages growing in response to local stimuli produce humoral substances, negatively affecting cellular-mediated defense and favoring elevated bacterial expansion in peritoneum.

Immunological Defenses in CAPD

“…This may cause a decreased production of stimulating factors (interleukin-1, leukotriene A) which could inhibit lympho-monocyte activation, thereby reducing the release of interleukin-2 and interferon-gamma. The sequence of these immunological events has been studied in our laboratory and the results confirm these pathophysiological hypotheses [27]. In patients with a high peritonitis incidence, the production of interferon-gamma by peri toneal lymphocytes and of interleukin-1 by peritoneal macrophages was significantly de creased, while the release of prostaglandin E2 was increased, when compared to CAPD pa tients with low rates of peritonitis or healthy subjects ( fig.…”

“…The above-mentioned studies have shown that in CAPD patients with a high peritonitis incidence the production of inter feron-gamma by peritoneal lymphocytes is reduced compared to the values observed in patients with a low peritonitis rate or in nor mal subjects [27], In trying to correct this (fig. 23).…”

Cytokine production by peripheral blood mononuclear cells from pediatric chronic peritoneal dialysis patients

“…Development of new connection devices has reduced the incidence of peritonitis considerably, but recurrent infection remains a significant source of morbidity and a frequent cause for termination of CPD. Because it had been previously reported that peritoneal macrophages from some CPD patients are deficient in their ability to produce inflammatory mediators such as cytokines, we examined the possibility that this defect might reflect a systemic defect in mononuclear cell function [1,2]. Although there was significant variability among patients, the median Sis for IL-I[~ and TNF-cz mRNA levels were similar for PBMC of CPD patients and controls, as were the amounts of stimulated TNF-cz protein secretion.…”

“…Peritoneal macrophages from some CPD patients have been shown to have a decreased ability to secrete cytokines such as interleukin-1 [3 (IL-I~) and tumor necrosis factor-ct (TNF-c0 [1,2]. These cytokines are critical to the development of an appropriate inflammatory response to bacteria and thus a defect in cytokine secretion by peritoneal macrophages could predispose a patient to develop peritonitis.…”