Related Experiment Videos
Prostaglandin E2 inhibits the release of tumor necrosis factor-alpha, rather than interleukin 1 beta, from human
M W Fieren1, G J van den Bemd, S Ben-Efraim
1Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Abstract:
We have reported previously that macrophages obtained from renal patients on continuous ambulatory peritoneal dialysis (CAPD) during an episode of infectious peritonitis display a decrease in intracellular cAMP levels and in spontaneous in vitro release of PGE2 and PGI2. Such macrophages also release large quantities of IL-1 beta and TNF alpha when stimulated in vitro by LPS. In view of the interregulatory effects between PGE2 and macrophage cytokines (IL-1 beta and TNF alpha) in their production, we examined in the present work to what extent the LPS-induced release of either IL-1 beta or TNF alpha in vitro from CAPD-originated peritoneal macrophages is affected by graded doses of exogenous PGE2 (range 0-1000 ng/ml) and by the cyclooxygenase inhibitor indomethacin (INDO) (10(-6) M). IL-1 beta and TNF alpha were determined using an enzyme-linked immunoabsorbent assay and an immunoradiometric assay, respectively. We found that PGE2 invariably induced a dose-dependent decrease in TNF alpha release. In peritoneal macrophages collected during an infection-free period, TNF alpha release decreased from 3225 pg/ml (controls) to 353 pg/ml at 1000 ng/ml of PGE2, and in peritoneal macrophages collected during an episode of infectious peritonitis, it decreased from 4100 pg/ml (controls) to 545 pg/ml at 100 ng/ml of PGE2. However, PGE2 failed to influence the secretion of IL-1 beta. INDO induced an approx. two-fold increase in TNF alpha release, but had no effect on IL-1 beta release. These findings indicate that exogenous and endogenous PGE2 controls the release of TNF alpha rather than IL-1 beta from LPS-stimulated peritoneal macrophages.
Insights
Prostaglandin E2 (PGE2) reduces tumor necrosis factor alpha (TNF alpha) release from peritoneal macrophages in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). This effect was observed in both infected and infection-free periods, highlighting PGE2
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Macrophages from renal patients on continuous ambulatory peritoneal dialysis (CAPD) during infectious peritonitis show reduced intracellular cAMP and spontaneous release of PGE2 and PGI2.
- These CAPD macrophages release significant amounts of IL-1 beta and TNF alpha when stimulated by LPS.
- Interregulatory effects exist between PGE2 and macrophage cytokines (IL-1 beta, TNF alpha).
Purpose of the Study:
- To investigate the impact of exogenous PGE2 and the cyclooxygenase inhibitor indomethacin (INDO) on LPS-induced IL-1 beta and TNF alpha release from CAPD-originated peritoneal macrophages.
Main Methods:
- Peritoneal macrophages were obtained from CAPD patients during infection-free periods and episodes of infectious peritonitis.
- Macrophages were stimulated with LPS and treated with varying doses of exogenous PGE2 (0-1000 ng/ml) or indomethacin (10(-6) M).
- IL-1 beta and TNF alpha levels were quantified using ELISA and IRMA, respectively.
Main Results:
- Exogenous PGE2 significantly decreased TNF alpha release in a dose-dependent manner in both patient groups.
- PGE2 did not affect IL-1 beta secretion.
- Indomethacin (INDO) approximately doubled TNF alpha release but had no impact on IL-1 beta release.
Conclusions:
- Exogenous and endogenous PGE2 primarily regulate TNF alpha release, not IL-1 beta, from LPS-stimulated peritoneal macrophages in CAPD patients.
- These findings elucidate a key mechanism in the inflammatory response during CAPD peritonitis.