Inhibition of interleukin-8 synthesis by intraarticular methotrexate therapy in patients with rheumatoid arthritis

5 Patients with definite RA and knee effusions under constant doses of DMARD therapy were treated with up to 6 intraarticular injections of 10 mg methotrexate (MTX) every 3 to 7 days. A matched randomized control group who received a single i.a. injection of 40 mg triamcinolone hexacetonide (TC) was monitored according to the same protocol. The intraarticular granulocyte counts and IL-8 levels decreased in all MTX treated patients on day 10-13 and stayed low in those patients who could be re-evaluated after 13 weeks. Compared to the IL-8 levels, the other tested cytokine levels showed only minor changes on day 10-13. There was no need for re-injection in the TC group during the 13 week study phase. We conclude that intraarticular MTX therapy results in a strong decrease of SF-granulocyte counts. This effect may be due to the impairment of IL-8 mediated chemotaxis by decreased IL-8 synthesis in synovial fluid mononuclear cells. Clinically, repeated intraarticular MTX therapy results in a worse 13 week outcome than i.a. steroid treatment measured in an intention-to-treat analysis.