Induction of T-kininogen and tumor necrosis factor-alpha by macrophage migration inhibitory factor in vivo

Administration of lipopolysaccharide (LPS) induces inflammation and tissue injuries that occasionally results in disseminated intravascular coagulatio n (DIC), This process is believed to be mediated by vasoactive molecules su ch as kinins and leads to endothelial damage and obstruction of the microci rculation. In this study, we evaluated the involvement of T-kininogen and m acrophage migration inhibitory factor (MIF) in endotoxin-induced systemic i nflammation. T-Kininogen is a protein unique to the rat and known as an acu te-phase protein in response to endotoxins. Similarly, MIF functions as a p roinflammatory cytokine and glucocorticoid-induced immunoregulator, First, we examined the effects of anti-MIF antibody on Wistar King male rats (ca 4 00 g) treated with intraperitoneal injection of LPS, At 6 hours after LPS i njection (5 mg/kg), the platelet counts had decreased from 85 +/- 12.8(x 10 (4)/mu L) to 8.8 +/- 2.6 (x 10(4)/mu L). We treated these rats with the ant i-rat MIF antibody (5 mg gamma G immunoglobulin [IgG] fraction/kg) 2 hours prior to LPS injection. This treatment prevented the decrease in platelet c ounts (45.6 +/- 5.6 [x 10(4)/mu L]). Next, we examined the potential of MIF for production of T-kininogen. Intraperitoneal injection of rat MIF signif icantly upregulated the serum content of T-kininogen at the dose of 500 mu g MIF/head. These results imply that MIF and T-kininogen might function in concert in the event of endotoxin-induced inflammation.