Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with rheumatoid arthritis.
Thromboxane and leukotrienes have been implicated in inflammation. However, the production level of these eicosanoids in patients with rheumatoid arthritis is still unclarified. In the present study, endogenous synthesis of thromboxane and cysteinyl leukotrienes in patients was investigated. The production of eicosanoids in patients is assessed by measuring stable urinary metabolites,11-dehydro thromboxane B2 and leukotriene E4, using gas chromatography/selected ion monitoring and liquid chromatography/tandem mass spectrometry. The level of urinary thromboxane in patients was significantly higher than that in healthy volunteers (P < 0.05). Furthermore, we investigated the effects of administered drugs on the production of these eicosanoids. The urinary thromboxane level of the untreated group (1630 +/- 613 pg/mg creatinine) was much higher than that of healthy volunteers (342 +/- 263 pg/mg creatinine). The level in the group receiving NSAID alone was similar to that in healthy volunteers, and the group receiving steroid alone showed slightly lower thromboxane levels than the untreated group. On the other hand, the leukotriene E4 level in patients (280 +/- 360 pg/mg creatinine) was also significantly higher than that in healthy volunteers (59 +/- 54 pg/mg creatinine, P < 0.05). In particular, the group receiving methotrexate (904 +/- 685 pg/mg creatinine) had higher leukotriene levels than not only healthy volunteers but also other medicated groups. These findings demonstrated that endogenous thromboxane and leukotriene production in patients with rheumatoid arthritis are enhanced, and the effects of medication on the production of these eicosanoids differed in thromboxane and leukotriene E4.
Nakamura
H
H
Department of Pharmaceutical Sciences, Tohoku University Hospital, Japan.
Hishinuma
T
T
Suzuki
N
N
Chiba
S
S
Tsukamoto
H
H
Takabatake
M
M
Sawai
T
T
Mitomo
T
T
Inoue
H
H
Matsumoto
F
F
Mizugaki
M
M
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000652:urine*; D003404:Creatinine / Q000652:urine; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008875:Middle Aged; D012016:Reference Values; D013256:Steroids / Q000627:therapeutic use; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013256:Steroids; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D003404:Creatinine