ABSTRACT
BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient's response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy. METHODS: This study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography-mass spectrometry (LC-MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes. RESULTS: Patients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24. CONCLUSIONS: Treatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Dimaprit/analogs & derivatives , Humans , Female , Prostaglandins , Antirheumatic Agents/therapeutic use , Tumor Necrosis Factor Inhibitors , Arthritis, Rheumatoid/drug therapy , Methotrexate , Certolizumab PegolABSTRACT
SJAMP and HLAMP are glucose-containing acidic mucopolysacc-harides isolated from sea cucumbers, Stichopus Japonicus and Holot-huria Lecospilota respectively. Their effects on the interaction of thrombin with endothelial cells were studied. Human vascular endothelial cells isolated from umbilical veins treated with 0.1% collagenasc were cultured with MEM medium. The contents of von Willebrand factor (vWF) and 6-keto-PGFla, stable hydrolysis product of PGI,, in the culture medium were measured with ELISA and immunoradioassay technique. The addition of thrombin to confluent monolayer endothelial cells resulted in a significant increase in the release of vWF and 6 ~ keto-PGFla in the culture medium. When heparin,SJAMP or HLAMP was added, no significant amount of vWF or 6~keto-PGFla could be detected in the medium .Whereas preincubation of thrombin with heparin, SJAMP or HLAMP respectively inhibited the thrombin-induced vWF and 6-keto-PGF 10 release and this effect was well correlated with the dose of heparin, SJAMP or HLAMP, indicating that SJAMP, HLAMP as well as heparin had inhibitory effect on the interaction of thrombin with endothelial cells
ABSTRACT
TxB2 and 6-keto-PGF1 alpha were determined in healthy persons, and their concentrations in plasma were 127?48 pg/ml(n = 40) and 138?77.9pg/ml(n = 36), respectively. We found that 6-keto-PG-F1 alpha levels in 156 specimens of the normal endomctriums elevated during secretive period, and the TxB2 also increased markedly during the menstrual period. Experimental DIC was induced by constant infusion of thrombin and EACA into the ear vein of the rabbits, and TxB2 and 6-keto-PGF1 alpha levels were increased at once in such instances. In 14 cases undergoing extracorporeal circulation, TxB2 was obviously enhanced during bypass and reached a peak value at 10 minutes of bypass, and then returned to the preopcrative level 2-4 hours after bypass, but there were no remarkable changes in 6-keto-PGF, alpha levels during bypass. The experimental results were discussed in the paper.
