6-ketoprostaglandin-f1-alpha and Arthritis--Rheumatoid

The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Age Factors; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Body Weight; Female; Flurbiprofen; Humans; Male; Metabolic Clearance Rate; Middle Aged; Prospective Studies; Thromboxane B2

The purpose of the current investigation was to study the influence of sulindac and naproxen on renal function and urinary excretion of the stable hydration product of prostacyclin, 6-keto-PGF1 alpha, in patients with arthritis and impaired renal function.. In a placebo-controlled, double-blind, cross-over design, the effects of 7 days of oral sulindac 200 mg twice a day were compared with naproxen 500 mg in the morning and 250 mg in the evening in 10 patients with polyarthritis and stable impaired renal function. Inulin and para-amino-hippurate sodium were used to calculate glomerular filtration rate and renal plasma flow. The excretion rate of 6-keto-PGF1 alpha was measured in urine collected overnight. After patients ingested drugs in the morning, urine was collected in fractions by spontaneous voiding. Venous blood samples were drawn repeatedly for assay of electrolytes, creatinine, proteins, hormones, and drugs. Grip strength and Ritchie articular index were recorded as indicators of symptomatic antiarthritic effectiveness.. Naproxen decreased urine levels of 6-keto PGF1 alpha by 59% (p less than 0.01). Sulindac had no effect on renal prostaglandin excretion. Naproxen reduced the glomerular filtration rate and renal plasma flow by 18% (p less than 0.05) and 13% (p less than 0.05), respectively, while no significant change was observed during the sulindac treatment periods. Serum levels of creatinine and complement factor D were unaffected by either drug. Plasma renin activity decreased during naproxen and sulindac treatments by 38% (p less than 0.05) and 22% (p less than 0.05). No significant change in plasma aldosterone was observed during the two drug treatments, but urinary aldosterone declined significantly (p less than 0.05) by 34% with naproxen. Albuminuria decreased (p less than 0.05) during both naproxen (41%) and sulindac treatment (72%), while the albumin/creatinine clearance ratio decreased by 59% (p less than 0.05) only during treatment with sulindac. N-acetyl-beta-D-glucosaminidase in urine was not changed by either drug. Sulindac and naproxen had no discernible effects on base excess, excretion of water, sodium, or potassium, or on osmolal clearance. However, serum potassium increased slightly but significantly (p less than 0.01) during treatment with naproxen. Sulindac sulfide, the active metabolite of sulindac, could not be traced in the urine from any of the patients. Mean arterial blood pressure declined significantly (p less than 0.05) during sulindac treatment but did not change during treatment with naproxen. Both drugs produced equal clinical improvement as measured by grip strength and the Ritchie articular index.. The results suggest that when sulindac and naproxen are given in clinical equipotent doses to patients with impaired renal function, sulindac does not affect renal prostaglandin synthesis or renal function, whereas naproxen induces suppression of renal prostaglandin synthesis and a further decrease in renal function.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Arthritis, Rheumatoid; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Naproxen; Placebos; Potassium; Renal Circulation; Renin; Sodium; Sulindac

Suprofen is a new potent analgesic with antiinflammatory properties that appears to inhibit prostaglandin synthetase in a tissue-selective manner, having relatively little effect on the kidneys of experimental animals. The effects were studied of one week of treatment of rheumatoid arthritis patients with suprofen or ibuprofen on Na+ and K+ excretion, creatinine clearance, urinary enzymes that are markers for tubular damage, and urinary prostaglandins such as PGE2 and 6-keto PGF1 alpha (a stable metabolite of prostacyclin). Neither compound caused changes in renal function related to the week of treatment, but significant decreases in prostaglandins were observed: this change was fully reversible after discontinuation of the drug.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Dinoprost; Double-Blind Method; Female; Humans; Ibuprofen; Kidney; Male; Middle Aged; Phenylpropionates; Prostaglandins F; Random Allocation; Suprofen

We investigated production of prostacyclin and the urinary ratio of thromboxane and prostacyclin in patients with rheumatoid arthritis. The prostacyclin production level was assessed according to the level of urinary 2,3-dinor-6-keto-prostaglandin F(1 alpha)measuring by gas chromatography/selected ion monitoring. In patients receiving medication, the prostacyclin level was lower and the thromboxane/prostacyclin ratio was greater compare with that of healthy volunteers. The prostacyclin level in patients without medication was approximately 4-fold higher than that of healthy volunteers and 8-fold higher than those of medicated groups. Although the ratio of the group without medication was similar to that of healthy volunteers, the urinary levels of each prostanoid were higher than those of other groups. Then, the ratios of groups receiving steroids were higher than that of other groups owing to high TX level. The present findings demonstrated that endogenous prostacyclin and thromboxane production increased in patients without medication, and prostacyclin production decreased with medication.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Arthritis, Rheumatoid; Chromatography, Gas; Creatinine; Epoprostenol; Female; Humans; Ions; Male; Middle Aged; Thromboxanes

Clinical and experimental evidence suggests that arachidonic acid metabolism through lipoxygenase and cyclooxygenase pathways may play an important role in the pathogenesis of both inflammatory and degenerative joint diseases. The aim of the present paper was to measure the levels of different arachidonate metabolites in arthrosis or rheumatoid joint effusions.. We studied synovial fluids from 22 patients with arthrosis and 8 patients with rheumatoid arthritis. The levels of TxB2, 6-keto-PGF1 alpha LTB4 and LTC4 were measured by radioimmunoassay.. The levels of the different arachidonate metabolites were higher in patients with rheumatoid arthritis than in those with arthrosis and the differences were always statistically significant, except for TxB2 values. Furthermore, in patients with arthrosis the levels of such metabolites were not significantly correlated with one another, with the exception of LTB4 and LTC4 values, while in patients with rheumatoid arthritis these levels were directly and significantly correlated.. In inflammatory joint disease levels of arachidonate metabolites are higher and more directly correlated with one another than in degenerative joint disease. Our data may explain the better efficacy of non-steroidal anti-inflammatory drugs in patients with arthrosis than in those with rheumatoid arthritis and the frequent necessity for steroidal treatment in this last condition.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arthritis, Rheumatoid; Humans; Joint Diseases; Leukotriene B4; Leukotriene C4; Radioimmunoassay; Synovial Fluid; Thromboxane B2

The pharmacological profile of a novel dual inhibitor, tepoxalin and of its carboxylic acid metabolite on cyclooxygenase and lipoxygenase pathways was evaluated by in vitro incubation with synovial tissue. Tissue specimens obtained at surgery in rheumatoid arthritis (RA, n = 10) or osteoarthritis (OA, n = 11) patients were incubated. Tepoxalin (10(-7), 10(-6), 10(-5) M) decreased eicosanoid release calculated in % of tyrode control for OA: LTC4 to 71-33%, 6-keto-PGF1a to 37-20%, PGE2 to 29-6%. For RA: LTC4 to 56-22%, 6-keto-PGF1a to 43-22%, PGE2 to 57-32%. Similarly, its metabolite (10(-7), 10(-5)M) decreased release in OA: LTC4 to 99 and 60%, PGE2 to 42 and 20%, 6-keto-PGF1a to 54 and 25%. In RA:LTC4 to 81 and 45%, PGE2 to 61 and 30%, 6-keto-PGF1a to 46 and 18%. Significance (P < 0.05) was achieved for all but 1 group (LTC4 metabolite at 10(-7)M vs tyrode). In summary a marked and dose dependent decrease of LT and PG release was obtained when incubating the dual inhibitor tepoxalin and its active carboxylic acid metabolite with synovial tissue at doses expected to be reached in the joint during therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Calcium; Dinoprostone; Eicosanoids; Humans; Leukotriene C4; Organ Culture Techniques; Osteoarthritis; Pyrazoles; Synovial Membrane

Twelve patients suffering from rheumatoid arthritis and having swollen knees were treated with 1.1 g/day of sodium naproxen administered in one dose, daily for 5 days. The 72-h wash-out period was verified by the absence of any nonsteroidal anti-inflammatory drug using a HPLC screening. Blood and synovial fluid samples were drawn just before treatment and 24 h after the last dose. Eicosanoids (PGE2, 6-keto-PGF1 alpha, TXB2, LTB4, LTC4) in synovial fluid were determined by immunoenzymatic assays. In plasma and synovial fluid, hyaluronic acid was assayed by radiometric assay and sodium naproxen by HPLC. Free drug was determined by equilibrium dialysis. Statistical analysis used nonparametric tests. Pain relief (evaluated on a visual scale), morning stiffness, and scores on the Lee and Ritchie indices all decreased significantly, as did PGE2 and LTB4 concentrations. The decrease in 6-keto-PGF1 alpha and TXB2 was not significant. No significant change was found for LTC4 and hyaluronic acid. Total concentrations of sodium naproxen were equivalent in plasma (16.1 micrograms.ml-1) and synovial fluid (18.9 micrograms.ml-1). Free fractions were significantly higher in synovial fluid (0.14%) than in plasma (0.11%), as shown by binding of the drug to human serum albumin, at various protein concentrations. Interestingly, the clinical efficacy, as shown by decreases in morning stiffness and in the Lee index score, correlated with the free concentration of naproxen in synovial fluid.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arthritis, Rheumatoid; Biomarkers; Chromatography, High Pressure Liquid; Dinoprostone; Female; Humans; Hyaluronic Acid; Immunoenzyme Techniques; Knee Joint; Leukotriene B4; Male; Middle Aged; Naproxen; Protein Binding; Synovial Fluid; Thromboxane B2

The effects of the inflammatory cytokines, tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1), and gamma interferon (IFN gamma) on macro- and microvessel-derived endothelial cell proteolytic, adhesion protein and prostaglandin synthetic activities were compared. TNF alpha treatment of human umbilical vein endothelial (HUVE) cells induced urokinase-type plasminogen (uPA) activity, increased HUVE uPA-dependent extracellular matrix (ECM) degradation, and accelerated matrix remodeling and endothelial differentiation into tubes or cord-like structures. All of the aforementioned effects of TNF alpha on HUVE uPA-dependent activities were abrogated by co- or pretreatment with IFN gamma. In contrast, endothelium derived from human lung (HLE) exhibited high constitutive uPA and uPA-dependent matrix degradation and rapid tube formation in Matrigel, activities all unaffected by TNF alpha or IFN gamma. Endothelium derived from human rheumatoid synovium (HSE) exhibited uPA-dependent activities intermediate between the HLE and HUVE. TNF alpha or IL-1 treatment of HUVE potently induced surface ICAM-1 expression, whereas these cytokines were relatively ineffective on HLE and HSE ICAM-1 expression. Co-incubation with IFN gamma synergistically elevated TNF alpha or IL-1 induced ICAM-1 expression in HUVE, HLE, and HSE. The major prostaglandin synthesized by HUVE was PGI2, in contrast to HLE and HSE which produced PGE2 as the major product. Although cytokine treatment increased prostanoid production in all three cell types, HLE were not responsive to IL-1, and HSE demonstrated the greatest increase in prostaglandin synthetic capacity. These studies underline important differences not only in the "constitutive" activities expressed by EC from different vascular beds, but also in the responsiveness to proinflammatory cytokines alone or in combination. These observations further emphasize the need to study the endothelial cell derived from the vascular bed of interest rather than extrapolate from results obtained with HUVE or other macrovessel-derived endothelium.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Arthritis, Rheumatoid; Cell Adhesion Molecules; Cells, Cultured; Child; Cornea; Dinoprostone; Endopeptidases; Endothelium, Vascular; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-1; Microcirculation; Pulmonary Circulation; Recombinant Proteins; Synovial Membrane; Tumor Necrosis Factor-alpha; Umbilical Veins; Urokinase-Type Plasminogen Activator

A limited number of experiments have shown that treatment of rheumatoid arthritis by means of cooling the entire body in cryogenic chamber reduces the pain in joints affected by inflammatory process and increases their mobility. The aim of the present thesis was to try explain the mechanisms responsible for the observed improvement of the patients' condition, and an investigation of the treatment's effect on selected hemodynamic indices. Tests were carried out on 63 patients with rheumatoid arthritis mainly in the 3rd and 4th stage of illness, all of whom had been treated for 14 days, once daily, by cooling the body for two-minute periods in cryogenic chamber with temperatures ranging from -110 degrees C to -160 degrees C, followed by kinesitherapy. It was demonstrated that after a single session in the cryogenic chamber, after 7 and 14 days the level of ACTH, cortisol and beta-endorphins in blood serum rises. The level of TSH, T4, T3, GH and 6-keto-PGF1 alpha+, however, remains unchanged. The cryogenic chamber treatment does not affect the heart rate, arterial blood pressure nor the value of the left ventricle fractional shortening index and its ejection, neither does it cause of arrhythmias and ischemic changes of the heart.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Female; Hemodynamics; Humans; Hydrocortisone; Hypothermia, Induced; Male; Middle Aged; Pituitary Hormones, Anterior; Thyroid Hormones; Time Factors

The effects of sulfasalazine (SASP) and its metabolites sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) were investigated on release of prostaglandins (PG) and leukotrienes (LT) from synovial tissue of 37 patients with osteoarthritis, chondrocalcinosis and rheumatoid arthritis. Calcium ionophore A23187 significantly increased the release of PGE2, 6-keto-PGF1 alpha, LTB4, and LTC4 from human synovial tissue irrespective of the underlying joint disease. SASP inhibited release of LTC4 and increased release of PGE2. On the other hand, 5-ASA and SP inhibited the release of all eicosanoids measured. The effective concentrations of SASP and SP were found to be in the range which can be reached during SASP therapy. On the other hand, blood and synovial fluid levels of 5-ASA are considerably lower than those which inhibit eicosanoid synthesis in vitro. While nonsteroidal anti-inflammatory drugs, which are used for symptomatic therapy of rheumatoid arthritis, inhibit cyclooxygenase only, SP, the active metabolite of the second line anti-rheumatic drug SASP, inhibits both PG and LT release. Inhibition of LT synthesis by SASP and SP could contribute to the second line efficacy of SASP therapy in rheumatoid arthritis.

Topics: 6-Ketoprostaglandin F1 alpha; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Chondrocalcinosis; Culture Techniques; Dinoprostone; Humans; Knee Joint; Leukotriene B4; Leukotrienes; Mesalamine; Osteoarthritis; Prostaglandins; SRS-A; Sulfapyridine; Sulfasalazine; Synovial Membrane

To evaluate the role of prostanoids in rheumatoid arthritis the effects of anti-inflammatory drugs on prostanoid concentrations and their ratios were studied in a primary culture of adherent synovial cells from patients with rheumatoid arthritis. Cells from rheumatoid synovium have a great capacity for prostanoid production. PGE2 is the main prostanoid but synovial cells are also capable of producing 6-keto-PGF1 alpha and PGF2 alpha. There were also very low TxB2 concentrations in the culture medium after incubation. All nonsteroidal anti-inflammatory drugs used (diclofenac, indomethacin and tolfenamic acid) reduced markedly, in concentrations achieved therapeutically (greater than or equal to 0.13 mumol/l), the production of all the prostanoids from endogenous substrate. There were no differences in the efficacity of the drugs. Hydrocortisone was needed for higher concentrations to inhibit PGE2, 6-keto-PGF1 alpha and PGF2 alpha production. TxB2 formation remained almost unaltered. After the drug incubation there were also clear alterations in the ratios between these prostanoids, which may have therapeutic importance. It is suggested that this kind of synovial cell culture can be used for testing the effects and mechanisms of different anti-inflammatory drugs in standardized cell culture conditions.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arachidonic Acids; Arthritis, Rheumatoid; Cells, Cultured; Dinoprost; Dinoprostone; Fatty Acids; Female; Humans; Hydrocortisone; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Prostanoic Acids; Synovial Membrane; Thromboxane B2

The effect of D-penicillamine (DPA) on immunoreactive prostanoid concentrations was studied in a primary culture of adherent synovial cells from patients suffering from rheumatoid arthritis (RA). DPA in clinically achievable concentrations increased the levels of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) and reduced those of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthetized from endogenous substrate. The capacity for PGE2 and 6-keto-PGF1 alpha production in the presence of exogenous arachidonic acid was decreased by DPA. These effects may be connected with the antirheumatic and immunosuppressive action of DPA.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arthritis, Rheumatoid; Cells, Cultured; Dinoprost; Dinoprostone; Female; Humans; Male; Middle Aged; Penicillamine; Prostaglandins; Prostaglandins E; Prostaglandins F; Synovial Membrane; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Arthritis, Rheumatoid; Dinoprostone; Fatty Acids, Unsaturated; Humans; Prostaglandins E; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arthritis, Rheumatoid; Eicosanoic Acids; Humans; Middle Aged; Thromboxane B2

The effects of one-day treatment with nine nonsteroidal anti-inflammatory drugs and prednisolone on human synovial fluid concentrations of prostanoids were studied. The doses were calculated so as to be approximately equipotent according to clinical experience and the recommendations of the manufacturers. Most of the drugs used reduced clearly PGE2 and TxB2 levels in synovial fluid, but only a slight diminution in 6-keto-PGF1 alpha values was found. Carprofen, diclofenac, indomethacin, naproxen and tolfenamic acid reduced significantly the synovial fluid PGE2 concentrations. Diclofenac and indomethacin also reduced significantly the synovial TxB2 concentrations.

Topics: 6-Ketoprostaglandin F1 alpha; Acetaminophen; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Carbazoles; Diclofenac; Dinoprostone; Guanidines; Humans; Indomethacin; Naproxen; ortho-Aminobenzoates; Prednisolone; Prostaglandins; Prostaglandins E; Quinazolines; Synovial Fluid; Thromboxane B2

Fibroblast-like synovial cells, isolated from intact joints of non-arthritic human donors and from explants of rheumatoid and non-rheumatoid synovial tissue, released prostacyclin (PGI2) when incubated in conditioned medium from human peripheral blood mononuclear cells (MCCM). The effect of MCCM on the rate of PGI2 synthesis (measured by radioimmunoassay as the stable product, 6-keto-PGF1 alpha) was clearly established within 2 h and appeared to require RNA and protein synthesis as judged by inhibition with actinomycin D and cycloheximide, respectively. Low concentrations of dexamethasone suppressed the increase in PGI2 levels. Prostaglandin E2 (PGE2) levels were also raised by the MCCM and reduced by dexamethasone. All-trans retinoic acid did not stimulate the levels of either prostanoid. These findings offer an explanation for some of the inflammatory events occurring in rheumatoid lesions.

Topics: 6-Ketoprostaglandin F1 alpha; Arthritis, Rheumatoid; Cell Line; Culture Media; Cycloheximide; Dactinomycin; Dexamethasone; Dinoprostone; Epoprostenol; Humans; Kinetics; Leukocytes; Prostaglandins E; Radioimmunoassay; Synovial Membrane; Tretinoin

Production of various arachidonic acid metabolites from both endogenous and exogenous substrate was measured using cultures of synovial fibroblasts from healthy and rheumatic synovia. At first, the rheumatic cells showed retarded growth and an altered histological picture. Rheumatic cells produced more 6-keto-PGF1 alpha, the main metabolite of prostacyclin, and prostaglandin E2 than did normal cells, which synthesized more thromboxane B2. Later on these differences diminished or disappeared, except regarding 6-keto-PGF1 alpha. When fairly high concentrations of exogenous arachidonic acid were used, for 2-hour incubation of the cells, the production of identified metabolites, 6-keto-PGF1 alpha, PGF2 alpha, PGE2, PGD2, PGA + PGB and thromboxane B2, was slightly less in rheumatic cells. In general, the main metabolite formed was 6-keto-PGF1 alpha. Some kind of feedback mechanism between prostaglandins and cyclic nucleotides is suggested.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Arthritis, Rheumatoid; Dinoprostone; Epoprostenol; Fibroblasts; Humans; In Vitro Techniques; Prostaglandins E; Synovial Membrane; Thromboxane A2; Thromboxane B2

Specimens of human rheumatoid and nonrheumatoid synovial lining were maintained in nonproliferative organ culture for 20 hours. The culture fluids were then assayed for prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)) by specific radioimmunoassay. The presence of each of these substances was confirmed by gas chromatography and mass spectrometry. Rheumatoid tissue produced significantly more of each cyclo-oxygenase product than nonrheumatoid tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Arthritis, Rheumatoid; Dinoprostone; Female; Humans; Male; Middle Aged; Organ Culture Techniques; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Synovial Membrane; Thromboxane B2; Thromboxanes

No significant differences were found in plasma concentrations and urinary excretion of prostaglandin E2 (PGE2), 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2), between rheumatoid arthritis patients and controls. However, urinary excretion of PGEe and 6-keto-PGF1 alpha tended to be greater and plasma levels of TxB2 lower in rheumatoid arthritis. Plasma concentrations and urinary excretion showed no marked circadian variation, although night or morning values were slightly lower. Plasma and urine prostaglandins do not correlate with clinical symptomatology in rheumatoid arthritis.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arthritis, Rheumatoid; Dinoprostone; Female; Humans; Male; Middle Aged; Prostaglandins E; Thromboxane B2; Thromboxanes

1 The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short-term treatment with 6alpha-methyl-prednisolone (6-MeP: 4-8 mg/day) or indoprofen (1.2 g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect.2 Measurements of prostaglandin E(2) (PGE(2)), thromboxane (TX) B(2), 6-keto-PGF(1alpha) and PGF(2alpha) were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity.3 PGE(2) and TXB(2) accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds.4 Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6-keto-PGF(1alpha) to 90% in the case of PGE(2).5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF(1alpha) concentrations were reduced by 35%, PGF(2alpha) concentrations were increased by 30%, while PGE(2) and TXB(2) were unchanged following 6-MeP.6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE(2) and TXB(2) levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti-inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side-effects.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Arthritis, Juvenile; Arthritis, Rheumatoid; Female; Humans; Indoprofen; Male; Methylprednisolone; Middle Aged; Phenylpropionates; Prostaglandins; Prostaglandins E; Prostaglandins F; Synovial Fluid; Thromboxane B2; Thromboxanes