Effects of dexamethasone, cyproheptadine, anisodamine, and dinoprostone onTNF alpha production in endotoxic shock

AIM: To study the effects of dexamethasone (Dex), cyproheptadine (Cyp), ani sodamine (Ani), and dinoprostone (Din) on lipopolysaccharides (LPS)-induced tumor necrosis factor alpha (TNFalpha) gene expression and antishock effec ts of inhibiting TNFalpha production. METHODS: Endotoxic shock in rats was produced by iv injection of LPS (E coli O111B4, 5 mg.kg(-1)). TNFalpha mRNA accumulation was assessed by Northern blot. Plasma TNFalpha contents were determined by radioimmunoassay. RESULTS: The TNFalpha mRNA levels in rat li ver at 2 h after LPS challenge was increased obviously (autoradiograms anal yzed by scanning were 38 +/- 10 vs saline control 1 +/- 8, P < 0.01). The p lasma TNFalpha contents were markedly increased [(22 +/- 3) mu g.L-1 vs sal ine control (2.2 +/- 1.0) mu g.L-1, P < 0.01]. Dex 5, Cyp 5, Ani 10, or Din 2 mg.kg(-1) immediately injected after iv LPS markedly decreased the TNFal pha mRNA levels in rat liver and plasma TNFalpha contents. The Dex, Cyp, An i, and Din improved the mouse survival rate 24 h after LPS 20 mg.kg(-1) cha llenge. CONCLUSION: Dex, Cyp, Ani, and Din strongly inhibit LPS-induced TNF alpha gene expression, and have a beneficial antishock effects.