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Interferon-gamma (IFN-gamma) as in vitro enhancing factor of peritoneal macrophage defective bactericidal activity
Abstract:
Interferon-gamma (IFN-gamma) can be considered a primary factor required in vitro and in vivo for inducing endocellular lysis of microorganisms by peritoneal macrophages (PM luminal diameter), an essential activity in continuous ambulatory peritoneal dialysis (CAPD) patients that prevents bacterial peritonitis. In 22 uremic patients treated with CAPD we analyzed: (1) the amount of IFN-gamma released by elicited peritoneal lymphocytes (PL); (2) oxidative metabolism and microbicidal activity by elicited PM luminal diameter; (3) immunoglobulin G (IgG) Fc-receptor expression on PM luminal diameter membrane; (4) the effect on PM luminal diameter hydrogen peroxide (H2O2) generation, bactericidal activity, and IgG Fc-receptor expression exerted in vitro by human recombinant IFN-gamma (rIFN-gamma). Results demonstrate that IFN-gamma release by elicited PL is lower in some CAPD patients with high peritonitis incidence (HPI) than in healthy donors or in CAPD patients with low peritonitis incidence (LPI). Simultaneously, PM luminal diameter from CAPD patients with HPI are characterized by a decreased ability to generate oxygen metabolites, to kill bacteria, and by a lack in IgG Fc-receptor expression; these defects were completely cured after being treated with rIFN-gamma. These results show that the IFN-gamma treatment in vitro could strengthen PM luminal diameter phagocytosis, oxygen metabolite generation, and bacterial killing in CAPD patients with HPI, and suggest that IFN-gamma may be considered a possible therapy in vivo for these patients.
Insights
Interferon-gamma (IFN-gamma) enhances peritoneal macrophage function in continuous ambulatory peritoneal dialysis (CAPD) patients. Supplementing with IFN-gamma may improve bacterial peritonitis defense in CAPD patients with high peritonitis incidence.
Area of Science:
- Immunology
- Nephrology
- Microbiology
Background:
- Peritoneal macrophages (PM) are crucial for controlling infections in continuous ambulatory peritoneal dialysis (CAPD) patients.
- Impaired PM function, including reduced microbicidal activity and immunoglobulin G (IgG) Fc-receptor expression, is linked to bacterial peritonitis in CAPD.
- Interferon-gamma (IFN-gamma) is known to enhance macrophage antimicrobial functions.
Purpose of the Study:
- To investigate IFN-gamma levels and peritoneal macrophage (PM) function in CAPD patients, particularly those with high peritonitis incidence (HPI).
- To evaluate the effect of human recombinant IFN-gamma (rIFN-gamma) on PM function in vitro.
- To explore the potential of IFN-gamma as a therapeutic agent for preventing bacterial peritonitis in CAPD patients.
Main Methods:
- Analysis of IFN-gamma release by peritoneal lymphocytes (PL) in 22 CAPD patients.
- Assessment of PM oxidative metabolism, microbicidal activity, and IgG Fc-receptor expression.
- In vitro treatment of PM with rIFN-gamma to assess its effects on H2O2 generation, bacterial killing, and Fc-receptor expression.
Main Results:
- CAPD patients with HPI exhibited lower IFN-gamma release from PL compared to healthy donors or low peritonitis incidence (LPI) patients.
- PM from HPI patients showed reduced oxygen metabolite generation, impaired bacterial killing, and decreased IgG Fc-receptor expression.
- In vitro treatment with rIFN-gamma completely restored PM phagocytosis, oxygen metabolite generation, and bacterial killing in HPI patients.
Conclusions:
- Reduced IFN-gamma production may contribute to impaired PM function and increased peritonitis risk in some CAPD patients.
- rIFN-gamma effectively enhances critical PM functions in vitro, suggesting its therapeutic potential.
- IFN-gamma therapy could be a promising strategy to bolster host defense against bacterial peritonitis in CAPD patients with HPI.
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