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Reduced secretion of IL-1 beta by peritoneal cells from patients on continuous ambulatory peritoneal dialysis
P H Hart1, C A Jones, K L Jones
1Department of Microbiology & Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
Abstract:
The endogenous and lipopolysaccharide stimulated interleukin (IL)-1 beta production in vitro by peritoneal monocytes/macrophages from patients on continuous ambulatory peritoneal dialysis (CAPD) was examined during episodes of infection and inflammation. Measurement of immunoreactive IL-1 beta and bioactive IL-1 in both supernatants and cell lysates after culture for 18 h revealed that these cells secreted a significantly lower proportion of total IL-1 than that measured for elutriated blood monocytes. For the inflammatory peritoneal cells, the proportion of total IL-1 beta that was cell-associated resembled that reported for more differentiated pulmonary alveolar macrophages and for adherent monocytes cultured for 18 h prior to stimulation. A similar reduced ability to secrete IL-1 beta was detected for unfractionated peritoneal cells from CAPD patients without peritonitis upon direct comparison with the IL-1 beta production by blood mononuclear cells from the same patients. These results suggested that at a time when a pro-inflammatory response by extravasated host monocytes/macrophages was required by CAPD patients with peritonitis, only a minor proportion of total IL-1 beta would be available extracellularly. This study highlights the rapidity with which extravasated monocytes lose their ability to secrete IL-1 beta and raises the possibility that an important site of utilization of IL-1 beta in vivo may be intracellular in its location.
Insights
Peritoneal monocytes/macrophages from continuous ambulatory peritoneal dialysis (CAPD) patients produce less interleukin (IL)-1 beta during infection. These cells rapidly lose their ability to secrete IL-1 beta, suggesting intracellular utilization in vivo.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Continuous ambulatory peritoneal dialysis (CAPD) patients are susceptible to peritonitis.
- Interleukin (IL)-1 beta is a key pro-inflammatory cytokine involved in immune responses.
Purpose of the Study:
- To investigate the production and secretion of IL-1 beta by peritoneal monocytes/macrophages in CAPD patients, particularly during infection and inflammation.
Main Methods:
- In vitro culture of peritoneal monocytes/macrophages from CAPD patients.
- Measurement of immunoreactive and bioactive IL-1 beta in cell supernatants and lysates.
- Comparison with blood monocytes and pulmonary alveolar macrophages.
Main Results:
- Peritoneal cells from CAPD patients secreted a significantly lower proportion of total IL-1 beta compared to blood monocytes.
- Inflammatory peritoneal cells showed a higher proportion of cell-associated IL-1 beta, similar to differentiated macrophages.
- Reduced IL-1 beta secretion was observed even in CAPD patients without peritonitis.
Conclusions:
- Extravasated monocytes/macrophages in CAPD patients rapidly lose their capacity to secrete IL-1 beta.
- A significant portion of IL-1 beta may be intracellularly located and utilized in vivo during peritonitis.