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BACKGROUND Inflammation is considered as one of the main pathogeneses in OA-induced pain. Macrophage migration inhibitory factor (MIF) is a well known pro-inflammatory cytokine. We aimed to determine whether MIF levels in serum and synovial fluid (SF) are associated with severity of OA-induced pain. MATERIAL AND METHODS We recruited 226 patients with knee OA and 106 controls. Self-reported pain severity of OA patients was evaluated using the Western Ontario McMaster University Osteoarthritis (WOMAC) pain scores. MIF levels were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS OA patients had similar serum MIF levels compared to controls (11.93 [5.68-18.10] vs. 10.06 [6.60-14.61] ng/ml, P&gt;0.05). In OA patients, MIF levels in SF were dramatically lower compared to paired serum samples (3.39 [1.87-5.89] vs. 11.93 [5.68-18.10] ng/ml, P&lt;0.01). MIF levels in SF were significantly correlated with WOMAC pain scores (r=0.237, P&lt;0.001), but MIF levels in serum had no significant correlation with WOMAC pain scores (r=0.009, P=0.898). CONCLUSIONS MIF levels in SF, but not in serum, were independently associated with the severity of self-reported pain in OA patients. The inhibition of MIF signaling pathways may be a novel therapeutic approach for ameliorating OA-induced pain.

Synovial Fluid Macrophage Migration Inhibitory Factor Levels Correlate with Severity of Self-Reported Pain in Knee Osteoarthritis Patients