thromboxane-b2 and Psoriasis

In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation and suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03228017.

Topics: Adult; Aspirin; Blood Platelets; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Endothelial Cells; Female; Humans; Male; Middle Aged; Platelet Activation; Platelet Adhesiveness; Psoriasis; Severity of Illness Index; Signal Transduction; Thromboxane B2; Treatment Outcome

Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect.. Our purpose was to assess the efficacy and safety of intravenously administered fish-oil-derived lipid emulsion on chronic plaque-type psoriasis.. A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a omega-3 fatty acid-based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional omega-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined.. The total PASI score decreased by 11.2 +/- 9.8 in the omega-3 group and by 7.5 +/- 8.8 in the omega-6 group (p = 0.048). In addition, the omega-3 group was superior to the omega-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the omega-3 emulsion and 9 of 40 patients (23%) receiving omega-6 fatty acid-based lipid emulsion. No serious side effects were observed. Within the first few days of omega-3 lipid administration, but not in the omega-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B5 and platelet thromboxane B3 generation occurred.. Intravenous omega-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation.

Topics: Adult; Arachidonic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fat Emulsions, Intravenous; Fatty Acids, Omega-3; Female; Follow-Up Studies; Humans; Leukotriene B4; Male; Middle Aged; Psoriasis; Thromboxane B2; Thromboxanes; Time Factors

Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Psoriatic; Double-Blind Method; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Leukotriene B4; Linoleic Acids; Male; Middle Aged; Neutrophils; Oenothera biennis; Plant Oils; Prostaglandins; Psoriasis; Severity of Illness Index; Thromboxane B2

Platelet-activating factor (PAF), as well as PAF acetylhydrolase (PAF-AH) activity in the peripheral blood plasma of patients with psoriasis and palmoplantar pustolosis, was measured with a radioimmunoassay technique, and compared with leukotriene (LT) B4, LTC4, LTD4 and E4 (LTD4/E4), thromboxane (TX) B2 and prostaglandin (PG) E2 levels. In a normal healthy group (n = 12) PAF level was 25.9 +/- 6.5 pg/0.1 ml plasma (mean +/- standard error of the mean: SEM), and this was elevated in patients with psoriasis (68.1 +/- 11.8, n = 25, P < 0.01), without a change in the PAF-AH level. LTB4 showed a similar increase (115.0 +/- 21.6 pg/ml vs. 68.2 +/- 11.8 pg/ml, P < 0.05), while TXB2 and PGE2 showed insignificant (P > 0.05) changes. LTC4 and LTD4/E4 were around the level of the limit of detection. Patients with palmoplantar pustulosis (n = 33) demonstrated similar, but milder and statistically insignificant, increases in PAF, LTB4, TXB2 and PGE2 levels. Modulation of the mediator levels before and after treatment was compared in 16 patients with psoriasis and 11 with palmoplantar pustulosis. PAF in psoriasis significantly decreased after treatment (70.9 +/- 17.1 to 25.1 +/- 5.5, P < 0.05) and this was moderately correlated (r = 0.298) with clinical improvement as indicated by the psoriasis area and severity index (38.5 +/- 7.5 to 10.9 +/- 4.2, P < 0.01). TXB2 (180.2 +/- 100.4 to 34.1 +/- 13.5), PGE2 (3.7 +/- 0.7 to 2.9 +/- 0.5) and LTB4 (120.1 +/- 31.1 to 84.2 +/- 8.2), in psoriasis, mildly decreased without statistical significance. Patients with palmoplantar pustulosis demonstrated a similar decrease in all mediators without statistical significance. The results obtained suggest a role of PAF in psoriasis. As the priming effects of PAF have been shown, for leucocytes and endothelial cells, to enhance their inflammatory response, we assume that PAF has roles in the acute phase of psoriatic and leucotactic inflammation.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adolescent; Adult; Aged; Arachidonic Acid; Child; Dinoprostone; Female; Humans; Leukotrienes; Male; Middle Aged; Phospholipases A; Platelet Activating Factor; Psoriasis; Thromboxane B2

Several reports have been published on platelet hyperaggregation in psoriatic patients, which might be related to alterations in arachidonic acid (AA) metabolism by platelets. We have studied the AA metabolism pattern, total eicosanoid formation and biosynthesis rate in platelet from psoriatic patients and from normal subjects after incubation with exogenous AA. We have found no difference in the metabolic pattern of platelets. Total formation of 12-HETE was higher in the control group (p less than 0.01). The rate of synthesis of cyclooxygenase products was higher in the psoriatic group, but only that of thromboxane B2 was statistically significant (p less than 0.02). There was a close correlation between thromboxane B2 formation rate and the lag time of platelet aggregation in response to 1 mM AA (p less than 0.01). The percentage of aggregation of platelets from psoriatics was significantly higher than that from normal subjects (p less than 0.05) and the lag time was lower in psoriatic group, but the difference was not statistically significant.

Topics: Adult; Arachidonic Acids; Blood Platelets; Chromatography, High Pressure Liquid; Eicosanoids; Female; Humans; Male; Middle Aged; Platelet Aggregation; Psoriasis; Thromboxane B2

The blood plasma levels of a number of endogenous prostaglandins have been measured by column chromatography followed by radioimmunoassay in 33 patients with psoriasis and in 22 children with allergic dermatoses. The findings evidence an increase of these prostanoids at the peak of the skin process exacerbation, thus indicating their role in the pathogenesis of psoriasis and allergic dermatoses in children.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Child; Child, Preschool; Chronic Disease; Dermatitis, Atopic; Humans; Infant; Middle Aged; Neurodermatitis; Psoriasis; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Blood Pressure; Cyclosporins; Dinoprost; Dopamine; Glomerular Filtration Rate; Humans; Kidney Transplantation; Prostaglandins; Prostaglandins F; Psoriasis; Regional Blood Flow; Thromboxane B2

Ten patients with psoriasis resistant to conventional topical treatment were given dietary supplements of fish oil, providing approximately 12 g of eicosapentaenoic acid daily for a period of at least 6 weeks. In eight patients there was a modest improvement in their psoriasis, the principal effects being a diminution of erythema and scaling. The dietary treatment resulted in a substantial inhibition of leukotriene B4 production by the peripheral blood polymorphonuclear leukocytes in vitro. The discrepancy between the high degree of inhibition of leukotriene B4 synthesis and the modest therapeutic effect suggests that leukotriene B4 is not the only mediator involved in the development of the psoriatic lesion. Furthermore, the in vivo cutaneous levels of leukotriene B4 might not have been inhibited to the same extent as the polymorphonuclear leukocyte levels in vitro. Further studies on the use of fish oil supplements, both on their own and in conjunction with other forms of treatment in psoriasis are warranted. It will also be important to determine whether the altered profile of 5-lipoxygenase products found in the blood is also seen in the skin.

Topics: Adult; Arachidonate 5-Lipoxygenase; Blood Platelets; Chromatography, High Pressure Liquid; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Unsaturated; Female; Fish Oils; Humans; Male; Middle Aged; Neutrophils; Psoriasis; Thromboxane B2