Ventilatory response to interleukin-1β in the rat: Role of glucocorticoids, nitric oxide, and eicosanoids

Interleukin-1β (IL-1β) induces transient monophasic increases in ventilation following i.v. administration. The role of glucocorticoid receptors, nitric oxide (NO), and eicosanoids in mediating the ventilatory response to i.v. IL-1β (75 ng/kg) was studied in chronically-instrumented unrestrained rats using wholebody plethysmography. Dexamethasone (DEX; n=5; 3 mg/kg i.v.), did not modify the ventilatory response to IL-1β (mean peak V̇ _E change 114.2 ± 27.0% [SD] pre-DEX vs. 152.6 ± 53.1% post-DEX, p - NS). L-NAME (n=9; 100 mg/kg), a non specific nitric oxide synthase inhibitor, decreased peak V̇ _E responses (126.6 ± 72.0% pre-L-NAME vs. 90.6 ± 31.0% post-L-NAME, p < 0.04). Indomethacin (IND; n=8; 1 mg/kg), a cyclo-oxygenase inhibitor, markedly attenuated the peak V̇ _E response (124.3 ±36.4% pre-IND vs. 76.3 ± 45.7% post-IND, p < 0.002). We conclude that NO and prostanoids play a role in IL-1β induced ventilatory increases, while glucocorticoid receptors do not appear to be involved. We speculate that prostaglandin E ₂ (PGE ₂) may mediate the ventilatory responses to IL-1β, and that nitric oxide may modulate PGE ₂ actions.