Macrophage colony stimulating factor involvement in uremic patients

Abstract

The immunodeficiency of patients with chronic renal failure (CRF) is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is recognized as a key factor in these immunological disorders. Since macrophage colony stimulating factor (M-CSF) is essential for the activation of several functions of monocytes and macrophages and their production of cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, we investigated its involvement in patients with CRF. When measured by ELISA, M-CSF serum levels were significantly higher in patients with progressive CRF and those on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate with the degree of renal insufficiency and were probably related to complex alterations in its production and/or degradation by the specific M-CSF receptors of macrophages. In HD patients the M-CSF serum concentrations inversely correlated with the number of circulating lymphocytes and were significantly higher in anemic patients requiring treatment with erythropoietin. Our results suggest that M-CSF may play a role in altering the immune system in uremic patients by maintaining in the circulation and tissues permanently primed monocytes and/or macrophages that can then be triggered to an activated state by secondary stimuli such as endotoxins, complement components, other cytokines or contact with foreign surfaces.

Expansion of CD14+CD16+ Blood Monocytes in Patients with Chronic Renal Failure Undergoing Dialysis: Possible Involvement of Macrophage Colony-Stimulating Factor

“…Other cytokines may contribute to the altered immune state associated with long-term HD. It has recently been reported that serum levels of M-CSF are significantly elevated in CRF patients and do not correlate with renal function [15]. The plasma levels of GM-CSF were also shown to be moderately increased in long-term HD patients [2].…”

“…We confirmed these findings in the present study, in which the plasma concentrations of M-CSF were significantly increased, whereas those of GM-CSF were slightly elevated in both HD and CAPD patients. The high serum levels of M-CSF in CRF patients are mainly a consequence of uremia [15]. This can be partially accounted for by monocyte activation resulting in the increased production of IL-1β and TNF-α, monocyte-stimulatory cytokines, through the autocrine loop.…”

Elevated SCF levels in the serum of patients with chronic renal failure

“…Previous reports have indicated that the levels of some haemopoiesis-associated growth factors and cytokines, such as macrophage colony-stimulating factor (M-CSF) (Kawano et al, 1993;Meur et al, 1996), interleukin (IL)-1beta (Herbelin et al, 1990) and IL-6 (Herbelin et al, 1991; …”

Antibody-Dependent Cellular Cytotoxicity in Patients on Chronic Hemodialysis

“…This increased absolute number of monocytes combined with the assumed preactivated status of monocytes could explain the observed superior IgG2-mediated ADCC capacity of DP's PBMC. An increased monocytic cell number in DP has been described before [35,36]. The mechanisms leading to increased monocyte counts in DP are still unclear, but systemic microinflammation and an altered cytokine environment, e.g.…”

“…The mechanisms leading to increased monocyte counts in DP are still unclear, but systemic microinflammation and an altered cytokine environment, e.g. elevated macrophage colony-stimulating factor [35,37] are likely to be responsible. …”