PubMed Health⌕ Search

Biomedical subjects

M W Fieren

Publications and source records attributed to M W Fieren.

18 recordsLinked to original sources
PubMed1996

Mechanisms regulating cytokine release from peritoneal macrophages during continuous ambulatory peritoneal dialysis.

The proinflammatory cytokines interleukin-1 (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are key mediators of the body's response to infection. Peritoneal macrophages from continuous ambulatory peritoneal dialysis (CAPD) patients isolated during peritonitis have an increased capacity to secrete IL-1 beta and TNF alpha. This peritoneal macrophage activation for IL-1 beta and TNF alpha release is a two-stage process. In contrast, peritonitis macrophages and infection-free macrophages stimulated in vitro with bacteria generate a decreased amount of the anti-inflammatory prostanoids. Exogenous and endogenous prostaglandin E2 (PGE2) was found to inhibit the release of TNF alpha rather than IL-1 beta from peritoneal macrophages, indicating that the synthesis and secretion of these cytokines is distinctly regulated by PGE2. In addition to macrophage products, acting in an autocrine fashion cytokine production and release may be regulated by secretory products of other cells in the peritoneal cavity including lymphocytes and mesothelial cells, which have the capability to produce various mediators. No evidence was found that the NO system is an important part of the antimicrobial arsenal of peritoneal macrophages.

Animals↗
PubMed1992

Prostaglandin E2 inhibits the release of tumor necrosis factor-alpha, rather than interleukin 1 beta, from human macrophages.

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.

Cells, Cultured↗
PubMed1992

Peritoneal macrophages from patients on continuous ambulatory peritoneal dialysis show a differential secretion of prostanoids and interleukin-1 beta.

In vitro secretion of the prostanoids PGE2 and PGI2 and of the cytokine IL-1 beta by peritoneal macrophages obtained from CAPD patients during episodes of peritonitis and infection free periods, was determined, after culturing with or without 5 micrograms/ml of LPS. The release of PGE2 and PGI2 as measured by its stable metabolite 6-keto-PGF alpha was determined in 10 episodes of peritonitis and 10 infection free periods. IL-1 beta release was determined in 14 episodes of peritonitis and 20 infection free periods. PGI2 release from macrophages declined sharply during peritonitis both in the absence and presence of LPS in the culture medium (p less than 0.005). A tendency to decreased PGE2 release was found during peritonitis, when macrophages were cultured in the absence of LPS. In the presence of LPS, the same amounts of PGE2 were released during peritonitis and during an infection free period. On the other hand, peritoneal macrophages released significantly more IL-1 beta during peritonitis as compared to an infection free period, provided that the cells were in vitro stimulated with LPS. In view of the interregulatory effects between prostanoids and macrophage cytokines in their production, these findings may indicate that the impaired release of PGI2 during peritonitis has allowed the macrophages to secrete more IL-1 beta after in vitro stimulation with LPS. This implies that PGI2 and PGE2 may play a distinct role in the regulation of cytokine secretion by these cells.

Dinoprostone↗
PubMed1991

[A patient with a wide aorta and 2 wide kidney pelves: retroperitoneal fibrosis].

The case is discussed of a patient with renal insufficiency due to severe stenosis of both ureters brought about by a periaortic inflammatory process. Such periaortitis is seen in severe atherosclerosis; the condition allegedly occurs in 5 to 23% of all patients with an abdominal aortic aneurysm. The literature on this form of retroperitoneal fibrosis is reviewed.

Aged↗
PubMed1991

Peritoneal macrophages from patients on continuous ambulatory peritoneal dialysis have an increased capability to release tumour necrosis factor during peritonitis.

We have reported previously that human peritoneal macrophages collected from patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) during an episode of peritonitis secrete increased amounts of interleukin-1 (IL-1), as compared to those collected during an infection free period, provided the cells were stimulated in vitro by LPS. We now report that such macrophages release also higher amounts of Tumor Necrosis Factor (TNF), if collected during peritonitis and stimulated subsequently in vitro by LPS. The increase in release of TNF was ascertained by radio-immunoassays as well as by bioassay of cytostatic effect against the highly sensitive TNF target-cell line L929 murine transformed fibroblasts. The present reported results, in addition to previously reported data on release of IL-1, indicate that induction of release of cytokines from human peritoneal macrophages is a dual stepwise process: first priming in vivo in an inflammatory environment and, secondly stimulation in vitro by LPS.

Adult↗
PubMed1990

Endotoxin-stimulated peritoneal macrophages obtained from continuous ambulatory peritoneal dialysis patients show an increased capacity to release interleukin-1 beta in vitro during infectious peritonitis.

Interleukin-1 (IL-1) release by peritoneal macrophages obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) was studied in nine patients during an infection-free period and eight patients during an infectious peritonitis, using an ELISA for IL-1 beta. Without exogenous stimulation with LPS, peritoneal macrophages from infected and uninfected patients released the same amounts of IL-1 beta, 183 +/- 40 pg ml-1 24 h-1) per 10(6) cells (means +/- SEM) and 251 +/- 96 pg ml-1, respectively. However, in response to a dose of 5 micrograms ml-1 of LPS, peritoneal macrophages released significantly more (P less than 0.005) IL-1 beta during peritonitis (6579 +/- 2793 pg ml-1 24 h-1 per 10(6) cells) compared with the infection-free period (1040 +/- 182 pg ml-1). These findings show that after microbial invasion of the peritoneal cavity, peritoneal macrophages are primed in vivo to release an increased amount of IL-1 beta in vitro after subsequent exogenous stimulation with LPS, indicating that peritoneal macrophage activation for IL-1 beta secretion occurs in steps.

Adult↗
PubMed1990

Peritoneal macrophages from patients on CAPD show an increased capacity to secrete interleukin-1 beta during peritonitis.

The in vitro release of interleukin-1 beta (IL-1 beta) by peritoneal macrophages from CAPD patients was studied during 16 infection free periods (16 patients) and 13 episodes of peritonitis (10 patients) using an ELISA. Without exogeneous stimulation with LPS, peritoneal macrophages released the same amounts of IL-1 beta. irrespective if they were obtained during an infection free period (473 +/- 92 pg/ml 24h, means +/- SEM) or during peritonitis (324 +/- 125 pg/ml). However, in response to a dose of 5 micrograms/ml of LPS, peritoneal macrophages released significantly more (p less than 0.005) IL-1 beta during peritonitis (6155 +/- 1743 pg/ml). These findings show that during peritonitis, peritoneal macrophages are primed in vivo to release more IL-1 beta in vitro after stimulation with LPS, indicating that activation of peritoneal macrophages for IL-1 beta secretion occurs stepwise.

Bacterial Infections↗
PubMed1985

Infectious-inflammatory changes in cyclic AMP levels and in their regulation by prostaglandins in human peritoneal macrophages.

Peritoneal macrophages of renal patients on continuous ambulatory peritoneal dialysis (CAPD) have been collected when CAPD was without complications, during an intercurrent infectious peritoneal inflammation and after recovery. Levels of cyclic AMP, release of cyclo-oxygenase metabolites, and responsiveness, in terms of cyclic AMP elevation, to either PGE2 or to DC-PGI2 (a stable analogue of PGI2) were examined. Peritoneal inflammation was associated with a sharp drop in cyclic AMP, which was restored after recovery. Production of TXA2, PGI2 and PGE2 parallelled the direction of changes in cyclic AMP levels, except, that release of PGE2 entirely failed to recover. Macrophages during the uncomplicated stage of CAPD proved more responsive to DC-PGI2 than to PGE2. During inflammation the cells displayed a marked increase in sensitivity towards PG stimulation. Improved sensitivity was more pronounced with PGE2 than with DC-PGI2 and so the original difference between responsiveness of the cells to the PGs was abolished. Several findings are compatible with the view that endogenous PGI2 governs the cyclic AMP levels in human non-inflammatory peritoneal macrophages. However, during infectious-inflammation the cells undergo changes which render a reduced production of PGI2 insufficient to explain the drop in cyclic AMP.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Cyclic AMP levels and their regulation by prostaglandins in peritoneal macrophages of rats and humans.

Basal levels of cyclic AMP and their alterations following stimulation by prostaglandins have been examined in rat peritoneal macrophages and in such cells of humans with renal disease on continuous ambulatory peritoneal dialysis (CAPD). Resident cells of rats contained more cyclic AMP than elicited macrophages, but the responsiveness to either PGE2 or DC-PGI2 (a stable synthetic analogue of PGI2) was higher with elicited than with resident cells. However, both kinds of peritoneal macrophages of rats were, in terms of cyclic AMP elevation, more sensitive to stimulation by PGE2 than by DC-PGI2. The CAPD macrophages of humans were elicited cells. The unstimulated levels of cyclic AMP in these human macrophages were much higher than those in elicited rat cells. Furthermore the human macrophages proved more sensitive to stimulation by DC-PGI2 than by PGE2. The reversed sensitivity, in comparison with rat cells, reflects the utterly poor effects of PGE2 in the human macrophages. The distinction in responsiveness to PGE2 and DC-PGI2 of the rat macrophages is compatible with the earlier reported distribution of and affinity to receptor binding sites of these PGs in the rat cells. The findings with the human macrophages suggest, however, that in these cells either the distribution of specific binding sites or the affinity of the two PGs to such sites might be substantially different from that of rats.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Clinical application of amikacin dosage based upon lean body mass in patients with different renal function.

To determine an adequate dosage of amikacin, a pharmacokinetic model was used based on lean body mass (LBM), age and serum creatinine. Amikacin was administered during a mean period of 7 days to patients with normal (group I, n = 15, CCr greater than 60 ml/min), impaired stable (serum creatinine within a range of 50 mumol/l), (group II, n = 10) and unstable (group III, n = 8) renal function. The mean trough and peak blood levels were less than 2 and 24, 4.5 and 25 and 7 and 26 micrograms/ml in groups I, II and III, respectively. In group II and III a maximum trough level of 10 instead of 5 micrograms/ml was permitted to prevent a prolonged period of low subtherapeutic levels. With this modification the regimen in both groups appeared satisfactory. The pharmacokinetic model allows an accurate dosage regimen in all groups and can easily be programmed into a pocket calculator.

Adolescent↗