Regulation of cytokine release from peritoneal macrophages of patients on continuous ambulatory peritoneal dialysis
Year: 1992
Type: dissertation
Abstract: The foundation of this thesis was laid in 1982 when we made the first\nstudies of the production of inflammatory mediators by macrophages\ncollected from effluent dialysate of patients on Continuous Ambulatory\nDialysis (CAPD).\nDuring the frrst experiments, these cells, harvested from infection-free\npatients, proved to be suitable for immunopharmacological studies (4).\nWhen macrophages were collected when CAPD was complicated by an\ninfectious peritonitis, the cells exhibited some striking differences in\ncomparison with macrophages that were collected when the patients were\ninfection-free. Notably the finding that the release of prostaglandins and\nthe intracellular cAMP levels were decteased in macrophages collected\nduring an episode of peritonitis, was intriguing (2). While prostaglandins\nare well known for their proinflammatory properties they can have antiinflammatory\nproperties as well thought to be mediated by stimulating\nintracellular cAMP levels (3). At that time emphasis was put on the\nproinflammatory properties of prostaglandins, while the relevance of t.l:te\nantiinflammatory properties to in vivo conditions was sometimes questioned.\nTne finding that macrophages from an inflammatory environment showed a decrease in the release of prostaglandins, might indicate, that\nprostaglandins fulfil antiinflammatory-immunomodulatory rather than\nproinflammatory functions with regard to these macrophages during the\nacute phase of an inflammation. A decrease in the release of the antiinflammatory\nprostaglandins could allow macrophages to become "activated"\nduring an infection (7). To test this postulate I proposed, in 1983, to\ni..-tvestigate the secretion of the proinfla.'lliDatory "factor" later identified as\ninterleukin-1: IL-l, by using peritoneal macrophages isolated from CAPD\npatients during peritoPitis and during an infection-free period. The\nfollowing questions had to be answered: 1) Is the decreased secretion of\nthe antii'l.flammatory prostaglandins, as found during peritonitis, associated\nwith increased secretion of the proinflammatory IL-l? 2) Do prostaglandins\nhave inhibitory effects on IL-l secretion? These questions underlie the\nstudies of this thesis.\nIL-l secretion by peritoneal macrophages from infected patients as compared\nto infection-free patients, is described in chapter 5.\nIn chapter 6, the relationship between the secretion of IL-lB and that of\nprostaglandins (PGEz, PGI:J was studied.\nIn chapter 7, the in vitro secretion of Tumor Necrosis Factor ex (TNFcx), an\nother cytokine with proinflammatory properties, by peritoneal macrophages\nfrom infected patients is compared with that of infection-free patients.\nTo what extent the release of IL-lB and TNFcx from peritoneal macrophages\nis affected by exogenous PGEz or the cyclooxygenase inhibitor\nindomethacin, is discussed in chapter 8.\nThese findi.'l.gs are summa.Tized in chapter 9. Furthermore the relevance of\nthese findings with regard to the acquisition of functional competence by\nperitoneal macrophages during infection, is discussed
Author: M. W. J. A. Fieren
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W44585951