Modification of airway histamine-receptor function with methylprednisolone succinate.

The purpose of the present study was to investigate whether glucocorticosteroids alter airway histamine-receptor function. We measured pulmonary resistance in six conscious sheep before and after inhalation challenge with 100 breaths of 5% histamine solution, without and with intravenous pretreatment with the specific H1- and H2-receptor antagonists. Inhalation of histamine (combined H1 and H2 stimulation) increased mean pulmonary resistance (RL) to 290% of baseline (p less than 0.05). Pretreatment with the H2 antagonist, metiamide (selective H1 stimulation), enhanced the effect of histamine, with a mean RL increase to 760% of baseline (p less than 0.05). Histamine challenge after pretreatment with the H1 antagonist, chlorpheniramine (selective H2 stimulation), decreased RL to 40% of chlorpheniramine value (p less than 0.05). A single intravenous bolus injection of methylprednisolone succinate (30 mg/kg) 30 min before histamine challenge suppressed the airway responsiveness to histamine, with a mean RL increase to only 186% of baseline. After methylprednisolone, selective H1-receptor stimulation with histamine elicited a blunted H1-receptor response; mean RL increased to only 248% of baseline. Both changes were significantly lower than that with histamine alone (p less than 0.05). Methylprednisolone per se blunted the chlorpheniramine-induced increase in RL which made it difficult to evaluate H2-receptor function (RL decreased to 67% of postchlorpheniramine value). However, in the presence of increased airway tone with carbachol, selective H2 stimulation with histamine decreased RL to 26% of postcarbachol value (p less than 0.05), thus excluding suppression of H2 receptors. Methylprednisolone had no effect on carbachol-induced increase in RL. In conscious sheep, methylprednisolone blunts airway responsiveness to histamine by suppressing H1 receptors without significantly altering H2 receptors or cholinergic-receptor function.