US EPA

1682980 

Journal Article 

Anti-inflammatory effects of verapamil and diltiazem in endotoxin-treated mice 

Hasko, G; Nemeth, Z; Vizi, ES; Szabo, C 

1996 

4TH INTERNATIONAL CONGRESS ON THE IMMUNE CONSEQUENCES OF TRAUMA, SHOCK AND SEPSIS: MECHANISMS AND THERAPEUTIC APPROACHES 

893-896 

WOS:A1996BH98U00159 

Intracellular calcium has been suggested to be an important mediator of the cellular response in endotoxemia. and shock. Here we have investigated the effect of the calcium antagonists verapamil (10 ms/kg i.p.) and diltiazem (20 mk/kg i.p.) on the endotoxin (lipopolysaccharide, LPS) induced production of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), interleukin-10 (IL-10) and nitric oxide (NO) in conscious mice. TNF plasma levels in control animals significantly increased at 60 min after LPS-injection (5 mg/kg), with a peak at 90 min, and return to basal levels al 180 min. LPS-induced TNF levels were significantly suppressed by pretreatment of the animals with both calcium entry blockers. The calcium entry blockers had no effect on LPS-induced IL-G plasma levels, but enhanced LPS-induced IL-10 production. In addition, the increase in plasma nitrite/nitrate levels, as measured at 8h after LPS, was not affected by verapamil and diltiazem pretreatment. Our data are in line with recent results showing that tile intracellular calcium mobilization inhibitor agent dantrolene also inhibits IL-l and TNF production in response to LPS. Thus, inhibition of calcium mobilization has pronounced anti-inflammatory actions by reducing the production of production of pro-inflammatory cytokines (but not of NO) and increasing the production of the anti-inflammatory IL-10 in endotoxin shock. 

Faist, E