A pathophysiological role of macrophage migration

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Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine released by macrophages, T-cells, and the pituitary gland during inflammatory responses. In order to clarify the pathophysiological roles of MIF in periodontal disease, we investigated relationship between MIF and a variety of inflammatory mediators, such as PGE_2, IL-6, TNF-α, and matrix metalloproteinase in gingival tissues. MIF was expressed in both normal and inflamed gingival tissues. Interestingly, LPS-injection led to increased serum levels of IL-6 (12.6 ± 4.2 ng/ml) and TNF-α (4.6 ± 3.8 ng/ml), although these cytokines were not detceted in normal rat serum (less than 30 pg/ml). However, MIF level was hardly increased by LPS injection (417.7±209.9 ng/ml in non-injection ; 427.1 ± 53.0 ng/ml in LPS-injection). On the other hand, it was clarified that MIF secretion seems to be due to mainly cell-death and subsequently leakage of intracellular MIF, by analyses of trypan blue exclusion, formazan formation, morphological changes, and Westren blot in human cultured fibroblasts stimulated with H_2O_2 and lipopolysaccharides. These results indicate that MIF secretion differs from other inflammatory cytokines such as IL-6 and TNF-α.