CALCIUM-ENTRY BLOCKERS INCREASE INTERLEUKIN-10 PRODUCTION IN ENDOTOXEMIA

Intracellular calcium is an important mediator of the cellular respons e in endotoxemia and shock. Here we investigated the effects of verapa mil and diltiazem, two calcium entry blockers, on endotoxin (bacterial lipopolysaccharide, LPS)-induced production of pro- and anti-inflamma tory cytokines and of nitric oxide in mice. LPS-induced interleukin-10 plasma levels were significantly enhanced, and circulating tumor necr osis factor-alpha concentrations were significantly suppressed in anim als pretreated intraperitoneally with verapamil (10 mg/kg) or diltiaze m (20 mg/kg). However, LPS-induced interleukin-6 levels were unaffecte d by the calcium antagonists. Similarly, LPS-induced production of nit rite/nitrate (breakdown products of nitric oxide) was not affected by verapamil and diltiazem. We conclude that calcium entry blockers selec tively modulate the production of some pro- and anti-inflammatory medi ators in endotoxemia. These effects may contribute to the cytoprotecti ve and anti-inflammatory effects of calcium entry blockers in shock an d trauma.