Steroids and antihistamines synergize to inhibit rat’s airway smooth muscle contractility

Abstract

Both glucocorticoids and H1-antihistamines were widely used on patients with allergic rhinitis (AR) and obstructive airway diseases. However, their direct effects on airway smooth muscle were not fully explored. In this study, we tested the effectiveness of prednisolone (Kidsolone) and levocetirizine (Xyzal) on isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of the drug were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine; (3) effect of the drug on electrical field stimulation (EFS) induced tracheal smooth muscle contractions. The result revealed sole use of Kidsolone or Xyzal elicited no significant effect or only a little relaxation response on tracheal tension after methacholine treatment. The tension was 90.5 ± 7.5 and 99.5 ± 0.8 % at 10(-4) M for Xyzal and 10(-5) M for Kidsolone, respectively. However, a dramatically spasmolytic effect was observed after co-administration of Kidsolone and Xyzal and the tension dropped to 67.5 ± 13.6 %, with statistical significance (p < 0.05). As for EFS-induced contractions, Kidsolone had no direct effect but Xyzal could inhibit it, with increasing basal tension. In conclusion, using glucocorticoids alone had no spasmolytic effect but they can be synergized with antihistamines to dramatically relax the trachea smooth muscle within minutes. Therefore, for AR patients with acute asthma attack, combined use of those two drugs is recommended.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle

“…Glucocorticoids alone had no anticholinergic effect, but that they could quickly relax the smooth muscle of the trachea when combined with antihistamines. In patients with allergic rhinitis with an acute asthma attack, using inhalation glucocorticoids and antihistamines simultaneously may be an option 25 .…”

Precision cut intestinal slices, a novel model of acute food allergic reactions

“…Thus, antihistamines were the drug of choice to demonstrate the utility of this ex vivo model for testing anti‐allergic therapeutics in development, as illustrated by the suppression of contraction responses. While anti‐allergic drugs are commonly tested in animal models, 44,55,56 the use of a human tissue‐based model either in place of or in addition to animal testing would allow for more translatable and clinically relevant results. Of note, the PCIS model has often been used to study pharmacokinetics in the context of human gut tissue 15–17,21,22 …”

Precision cut intestinal slices, a novel model of acute food allergic reactions

“…Thus, antihistamines were the drug of choice to demonstrate the utility of this ex vivo model for testing anti-allergic therapeutics in development, as illustrated by the suppression of contraction responses. While anti-allergic drugs are commonly tested in animal models, 41,54,55 the use of a human tissue-based model either in place of or in addition to animal testing would allow for more translatable and clinically relevant results. Of note, the PCIS model has often been used to study pharmacokinetics in the context of human gut tissue.…”