Interferon-gamma levels in peritoneal dialysis effluents: Relation to peritonitis

Abstract

As peritoneal macrophages require Interferon-gamma (IFN-gamma) for bacterial lysis, IFN-gamma levels were measured in peritoneal dialysis effluents. (PDE) by a specific radioimmunoassay. High IFN-gamma levels were found in patients with peritonitis compared to low levels in patients without peritonitis (mean 9.73 +/- 2.63 SE U/ml, N = 39 vs. 0.25 +/- 0.04, N = 32). IFN-gamma levels varied among different bacteria: Staph. aureus (highest: 23.4 +/- 5.7, N = 14), Staph. epidermidis (lower: 3.2 +/- 0.8, N = 13), other gram-positive (1.06 +/- 0.32, N = 6), gram-negative bacteria (lowest: 0.57 +/- 0.30, N = 6). After treatment of peritonitis levels decreased. In corresponding blood and PDE samples, by comparing IFN-gamma levels in 10 peritoneal dialysis patients (5 with peritonitis, 5 without), levels were raised only in PDE of patients with peritonitis, implying local IFN-gamma production. Total lymphocytes, T, B and monocyte subsets in patients' plasma and PDE did not differ, except for a higher number of mononuclear cells in PDE of patients with peritonitis (P < 0.05). Further investigation of in vitro IFN-gamma production in PDE with peritoneal monocytes, syngeneic host lymphocytes, and bacteria showed that Staph. aureus induced the highest levels of IFN-gamma and E. coli the lowest, in experiments with T cell enriched host lymphocytic fractions. We conclude that Staph. aureus peritonitis induces high levels of IFN-gamma in PDE, possibly by a T cell dependent superantigen response.

IL-17 Stimulates Intraperitoneal Neutrophil Infiltration Through the Release of GROα Chemokine from Mesothelial Cells

“…A broad spectrum of effects exerted by lymphocyte-derived mediator IFN-␥ (12) points to a significant role of lymphocytes in the inflammatory response. In this respect, increased levels of IFN-␥ have been detected in the inflamed peritoneum, and this rise has been clearly attributed to peritoneal lymphocytes (13).…”

Characterization of human peritoneal dendritic cell precursors and their involvement in peritonitis

“…Second, the presence of this population provides a unique experimental setting to study DC biology especially as it relates to in vivo and in situ differentiation of these cells. Previous studies have shown that PD-related peritonitis correlates with increased levels of IFN-g levels in the peritoneal effluent, implying that the predominant adaptive immune response to peritoneal infection is cell-mediated [14,15]. DC play a critical role in the initiation of such a response by uptaking antigens from the aetiological pathogen and subsequently migrating to nearby secondary lymphoid tissues to activate T cells.…”

“…In addition, we demonstrate that the entire peritoneal pool of CD14 + mononuclear cells have the capacity to differentiate into DC or macrophages in vitro , under appropriate conditions, indicating that these cells are not fully differentiated despite their location in peripheral tissues. These data provide a mechanistic explanation for the predominant Th1 environment observed during episodes of PD-related peritonitis [14,15].…”

Differential Regulation of Chemokine Production in Human Peritoneal Mesothelial Cells: IFN-γ Controls Neutrophil Migration Across the Mesothelium In Vitro and In Vivo

“…We have examined the regulatory effects of IFN-␥ on constitutive as well as proinflammatory cytokine (IL-1␤ and TNF-␣)-induced HPMC-chemokine production with doses of cytokines known to be present in the peritoneal cavity during bacterial peritonitis (14,15). Our in vitro culture studies show that IFN-␥ alone was an efficient stimulus for MCP-1 production, and the combination of IFN-␥ with IL-1␤ (or TNF-␣) resulted in significant synergistic up-regulation of MCP-1 synthesis.…”

“…cytokine levels during peritoneal dialysis-associated peritonitis suggests that i.p. elevation of the T cell-derived cytokines IFN-␥, IL-2, and IL-10 occur during infection (14,15). Recent in vitro studies indicate that IFN-␥ is capable of modulating both CXC and CC chemokine secretion in a number of cell types, data that suggest that it plays a central role in controlling leukocyte influx (16 -18).…”