Analysis of urinary prostacyclin and thromboxane/prostacyclin ratio in patients with rheumatoid arthritis using gas chromatography/selected ion monitoring T. Hishinuma, 1 H. Nakamura, 1 T. Sawai, 2 T. Mitomo, 3 H. Inoue, 4 F. Matsumoto, 5 M. Mizugaki 1 1 Department of Pharmaceutical Sciences,Tohoku University Hospital, 2 First Department of Pathology, Iwate Medical University, 3 Rheumatology Center,Tohoku Koseinenkin Hospital, 4 Division of Orthopedics,Tohoku Rosai Hospital, 5 Division of Orthopedics, Naruko National Hospital, Japan Summary 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 1a 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 highTX level.The present findings demonstrated that endogenous prostacyclin and thromboxane production increased in patients without medication, and prostacyclin production decreased with medication. & 2001Harcourt Publishers Ltd INTRODUCTION Rheumatoid arthritis (RA) is a disease that causes inflam- mation at various joints in the whole body, and the joint is destroyed by abnormal multiplication of synoviocytes. In the inflammatory joint, cyclooxygenase (COX)-2 is induced in the synoviocyte, cartilage and inflammatory monocyte, 1,2 and various prostanoids such as prostaglandin (PG) E 2 , PGF 2 , prostacyclin (PGI 2 ) and thromboxane (TX) are released from the synoviocyte and other tissue. 3–5 PGE 2 is related to not only inflammation but also joint destruction by stimulating bone resorption. 6,7 The role and production levels of other prostanoids in RA patients remains unclear. In a previous study, we determined the urinary level of 11- dehydro-TXB 2 , the major urinary metabolite of TXA 2 , in RA patients and showed that the levels of TX were higher than that of healthy volunteers and altered by medication and surgery. 8 Recently, it was reported that arachidonic acid is preferentially metabolized to PGI 2 and PGE 2 by COX-2 in rat peritoneal macrophages. 9 Furthermore, the action of PGI 2 during inflammation has been extensively investigated since a study demonstrated that mice lacking prostacyclin receptor (IP receptor) differed from normal mice in pain perception and inflammatory response. 10 These suggested that prostacyclin plays an important role in inflammatory diseases. In the present study, we investigated the endogenous production level of PGI 2 in the same urine sample of RA patients used in our previous study of TX Prostaglandins, Leukotrienes and Essential Fatty Acids (2001) 65(2), 85^90 & 2001 Harcourt Publishers Ltd doi:10.1054/plef.2001.0293, available online at http://www.idealibrary.com on Correspondence to : Michinao Mizugaki, Department of Pharmaceutical Sciences,Tohoku University Hospital,1-1 Seiryo-machi, Aoba-ku, Sendai 980- 8574, Japan. Tel.: 81 22 717 7525; Fax: 81 22 717 7545; E-mail: mizugaki@mail.cc.tohoku.ac.jp Grants: The Health Science Research Grants for the Research of Pharmaceutical and Medical Safety from the Ministry of Health and Welfare of Japan and Research on Health Sciences Focusing on Drug Innovation from the Japan Health Sciences Foundation. Received 2 March 2001 Accepted 25 May 2001 & 2001Harcourt Publishers Ltd Prostaglandins, Leukotrienes and Essential FattyAcids (2001) 65(2), 85^90