Inflammatory fluids regulate TNF-alpha, but not IL-1 beta, production by human peritoneal macrophages. A study of patients on continuous ambulatory peritoneal dialysis with peritonitis.
To gain insight into the factors regulating an inflammatory response in vivo, the activities of peritoneal macrophages and the influence of the inflammatory fluids from which they were harvested were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis. Specifically, the production of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and prostaglandin E2 (PGE2) by lipopolysaccharide-stimulated human peritoneal macrophages from CAPD patients with peritonitis was examined in the presence of the inflammatory dialysates from which they were isolated. When tested at a dilution of 20%, the dialysates inhibited production of TNF-alpha, a key monokine in the orchestration of the inflammatory response. In contrast to the effect on TNF-alpha, the dialysates did not affect IL-1 beta production by stimulated macrophages. The activity inhibitory for TNF-alpha synthesis was not fully characterized, but a number of known inhibitors were shown not to be responsible for the suppressive activity. The inhibitory activity was detected in cases of noninfective peritonitis and excluded the possibility that a bacterial product was responsible. Hyperosmolality, pH, protein levels, glucose, uremic molecules, cortisol, heparin, and antibiotics were not responsible for the inhibitory activity. The activity had some similarity to the reported actions of alpha-globulins (which are acute phase proteins), PGE2, TNF-alpha soluble receptors, and IL-6, but there was no evidence for their involvement. Whether the selective suppression of TNF-alpha production is a general finding in inflammatory responses will require additional studies. This study nevertheless illustrates the potential for the host to regulate tightly the development of an excessive inflammatory response and thus to limit tissue pathology. However, it is unknown whether an appropriate host defense is compromised.
Hart
P H
PH
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
Jones
C A
CA
Finlay-Jones
J J
JJ
D000209:Acute-Phase Proteins / Q000494:pharmacology; D000302:Adrenal Cortex / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001770:Blood Bactericidal Activity / Q000187:drug effects; D003404:Creatinine / Q000032:analysis; D015232:Dinoprostone / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D009994:Osmolar Concentration; D010529:Peritoneal Cavity / Q000166:cytology*; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010538:Peritonitis / Q000209:etiology; D011506:Proteins / Q000032:analysis; D011956:Receptors, Cell Surface / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014508:Urea / Q000032:analysis; D014511:Uremia / Q000378:metabolism; D014527:Uric Acid / Q000032:analysis
D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D015850:Interleukin-6; D011506:Proteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid; D014508:Urea; D006493:Heparin; D003404:Creatinine; D005947:Glucose; D015232:Dinoprostone; D006854:Hydrocortisone