Diversity in peritoneal macrophage response of CAPD patients to 1,25-dihydroxy vitamin D3

Abstract

A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis. Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection. The effect of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] on the activity of peritoneal macrophages from CAPD patients and nonuremic controls was studied. 1,25(OH)2D3 had a biphasic effect on superoxide generation in the concentration range of 2.5 10(-9) M to 5 x 10(-6) M with a peak at 2 x 10(-8) M. The addition of 2 x 10(-8) M 1,25(OH)2D3 to nonuremic control macrophages for 24 hours caused a significant twofold increase in superoxide generation in response to phorbol myristate acetate (PMA), from 2.21 + 0.2 to 4.1 + 0.2 nmol/10(6) mac (P less than 0.001), and enhanced the bactericidal activity from 60 + 7% to 85 + 9% (P less than 0.005). CAPD patients were divided into two groups: Group A, patients with high peritonitis incidence (HPI); group B, patients with low peritonitis incidence (LPI). Macrophages from HPI patients show a lower bactericidal activity (37 +/- 5%) and were not affected by 1,25(OH)2D3 after 24 hours of treatment. The increase in macrophage activity was seen only after three days of incubation with the hormone. Macrophages from this group generated a high amount of prostaglandin E2 (PGE2) during the first 24 hours in culture (7.8 +/- 0.52 ng/ml as compared with 0.35 +/- 0.03 ng/ml in the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Risk Factors for Peritoneal Dialysis–Associated Peritonitis: The Role of Oral Active Vitamin D

“…In a study by Carozzi et al, calcium and 1,25-dihydroxycholecalciferol enhanced the antimicrobial function of macrophages isolated from PD patients in vitro (30). These results were confirmed by Levy et al, who showed that treatment of peritoneal macrophages with 1,25-dihydroxycholecalciferol increased superoxide generation and bactericidal activity (31). Furthermore, the activation of the intracellular antimicrobial peptide cathelicidin in monocytes and macrophages by toll-like receptors is vitamin D 3 -dependent (32), which leads to enhanced killing of intracellular Mycobacterium tuberculosis (33).…”

Effect of 1,25-Dihydroxyvitamin D on the Immune Activity of Peritoneal Macrophages in Continuous Ambulatory Peritoneal Dialysis Patients

“…Consequently, studies were conducted in order to es tablish whether l,25(OH)2D3 is capable o f modulating peri toneal macrophage function. We were able to prove that pe ritoneal macrophages from CAPD patients were indeed a target for l,25(OH)2D3 and that this vitamin D metabolite markedly enhanced functions such as generation of super oxide and the killing capacity of these cells [24], A recent publication, in which the function of peripheral polymor phonuclear leukocytes and monocytes in patients on hemo dialysis was investigated before and after l,25(OH)2D3 treatment, supports our findings [25].…”

“…This finding strongly sup ports the hypothesis that a humoral factor present in the pe ritoneal effluent of CAPD endows the peritoneal macro phages with the ability to metabolize 25-OH-D, to 368 Shany/Levy/Chaimovitz V itam in D in C A P D l,25(OH)2D3. Prostaglandins present in the peritoneal dialysate may be involved in this process since PGE2 stimulated, and indomethacin markedly suppressed l,25(OH)2D3 syn thesis by macrophages [24,30]. Moreover, we and other in vestigators have been able to demonstrate that the metabo lism o f 25-OH-D, was significantly enhanced in cells har vested from CAPD patients during episodes of bacterial peritonitis [30,40].…”

“…Moreover, we and other in vestigators have been able to demonstrate that the metabo lism o f 25-OH-D, was significantly enhanced in cells har vested from CAPD patients during episodes of bacterial peritonitis [30,40]. Indeed, the PGE2 concentration in CAPD fluid obtained from CAPD patients suffering from peritonitis was found to be much higher than the concentra tion of PGE2 in the dialysate of noninfected patients [24].…”

The Peritoneal Immune System and Continuous Ambulatory Peritoneal Dialysis

“…We have shown that PMΦ from CAPD patients are capable of metabolizing 25-hydroxyvitamin D to 1,25-(OH) 2 D 3 in vitro [16]. This property was not found in PMΦ from normal subjects, but incubation of normal PMΦ with peritoneal effluent from CAPD patients induced the ability in these cells to metabolize vitamin D. This ability may be related to the bactericidal activity of PMΦ, since it was found that incubation of normal PMΦ with 1,25(OH) 2 D 3 caused a significant twofold increase in superoxide generation in response to phorbol myristate acetate and enhanced bactericidal activity [17]. Interestingly, PMΦ from patients with a high incidence of peritonitis showed a low bactericidal activity and were not affected by 1,25(OH) 2 D 3 after 24 h of treatment.…”