Infliximab治療による関節リウマチ患者の抑うつ状態改善の機序  [in Japanese] Mechanism of Improvement of Symptoms of Depression in Patients with Rheumatoid Arthritis Treated with Infliximab  [in Japanese]

目的:関節リウマチ(RA)患者の約14〜42%は抑うつ傾向があり,一方infliximabはRA対する有効性が高く,RA患者の抑うつ状態も改善させることを報告した.その機序についてサイトカイン,ホルモンの測定も含めて検討した.方法:Infliximab治療RA患者20例に対し,治療開始前,開始14,30週後にself-rating depression scale (SDS)を施行し,治療開始前と比較した.RAの疾患活動性はdisease anxiety score 28 (DAS28ESR4),QOL評価はmodied health assessment questionnaire (mHAQ)を使用した.同時に抑うつ状態と関連のあるサイトカインとしてtumor necrosis factor (TNF)-α,interleukin (IL)-6,ホルモンはdehydroepiandrosterone-salfate (DHEA-S)を測定し,欧州リウマチ学会改善基準別に層別解析を行った.結果:Moderate response以上の反応群においては,無反応群と比較すると治療開始前のTNF-α,IL-6は高く,治療開始14,30週後のSDS,mHAQは改善,TNF-α,IL-6,DHEA-Sは低下傾向であった.しかし,無反応群では治療開始後のTNF-αは上昇し,IL-6は一定の傾向を示さず,SDS,mHAQ,DHEA-Sはほとんど変化しなかった.結論:Infliximab治療が有効なRA患者では,TNF-α,IL-6,DHEA-Sの低下を介して抑うつ状態が改善する可能性が考えられた.

Objective: Infliximab therapy effectively suppresses disease activity and improves symptoms of depression in patients with rheumatoid arthritis (RA). To elucidate the medication's mechanism, we examined changes in tumor necrosis factor (TNF)-α, interleukin (IL)-6 and dehydroepiandrosterone-salfate (DHEA-S). Method: Self-rating Depression Scale (SDS), serum concentrations of TNFα, IL-6 and delta DHEA-S were assessed in 20 patients with RA, at baseline and after 14 and 30 weeks of Infliximab treatment. (Delta DHEA-S rather than DHEA-S was measured because normal values of the latter vary depending on age and sex.) Disease activity was evaluated with the disease activity score 28 (DAS28). Quality of life was evaluated with the modified health assessment questionnaire (mHAQ). Results: Serum levels of both TNFα and IL-6 were elevated before Infliximab treatment in the patients with a moderate to high improvement in response to Infliximab treatment. Total scores on the SDS and mHAQ were improved and the serum levels of delta DHEA-S also decreased. On the other hand, patients with no response to treatment had lower TNFα and IL-6 levels at baseline and no significant change in total scores on the SDS and mHAQ. After treatment, serum levels of TNFα were slightly increased, while IL-6 showed no significant change and delta DHEA-S decreased slightly. Conclusion: Infliximab may improve depression in patients with RA by suppressing the expression of TNFα, IL-6 and DHEA-S.