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Sustained changes in lipid profile and macrophage migration inhibitory factor (MIF) levels after anti-TNF therapy in rheumatoid arthritis.

Wijbrandts CA, van Leuven SI, Boom HD, Gerlag DM, Stroes ES, Kastelein JJ, Tak PP.

Academic Medical Center/University of Amsterdam, Netherlands.

BACKGROUND: Macrophage migration inhibitory factor (MIF) has recently emerged as an important cytokine possibly linking rheumatoid arthritis (RA) and atherogenesis. Because atherogenesis is accelerated in RA we investigated whether anti-TNF therapy could lead to sustained downregulation of systemic MIF levels and improvement of lipid profiles. METHODS: Fifty RA patients with active disease (disease activity score 28 (DAS28 "d 3.2)), who started adalimumab therapy 40 mg every other week, were included. At baseline, week 16 and 52 serum levels of MIF and lipids were assessed. In addition, the DAS28 and serum C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were determined. RESULTS: After 16 weeks of adalimumab therapy, both DAS28 and MIF levels were significantly decreased (P < 0.001 and P = 0.020, respectively). This was sustained up to week 52 (P < 0.001 and P = 0.012, respectively). CRP levels and ESR were significantly reduced after 16 and 52 weeks of adalimumab therapy (P < 0.001). HDL cholesterol levels increased at week 16 (P < 0.001), but returned to baseline at week 52. Apo A-I levels increased at week 16 (P <0.001) and remained stable (P = 0.005). This resulted in an improved apo B/ A-I ratio. CONCLUSIONS: Our results underline sustained downregulation of MIF as a potential new mechanism by which anti-TNF therapy might reduce vascular inflammation, and as such perhaps cardiovascular morbidity in RA patients. This hypothesis is supported by an improved apo B/ A-I ratio as well as reduced CRP levels in our patients.

PMID: 18723565 [PubMed - as supplied by publisher]