Related Experiment Videos
Histamine-induced mucociliary dysfunction and otitis media with effusion
1Department of Otolaryngology, Osaka City University Medical School, Japan.
Abstract:
Histamine, which has been found in middle ear effusions, is a potent pharmacological mediator released at an early stage of allergic reactions or general inflammatory process, increasing permeability of small blood vessels. Histamine might be involved in the origin and chronicity of middle ear effusions. In this study we studied the effect of histamine on the mucociliary function. First we examined the effect of histamine and its H1 and H2 blockers on the ciliary activity in the middle ear. 10(-2) M of histamine deteriorated ciliary activity; however, at lower concentrations ciliostimulatory effects were demonstrated for histamine (between 10(-8) M and 10(-4) M). Such ciliostimulatory effects were not affected by diphenhydramine (H1-blocker) but were reduced by cimetidine (H2-blocker). Thus histamine stimulates ciliary activity by combining with H2-receptor. Intratympanic injection of 10(-4) M of histamine induced accumulation of middle ear effusions (MEEs). The volume of MEEs was largest at 1 day postinjection when its mucociliary clearance time was longest. Then the mucociliary clearance time became shorter, but it was still significantly longer than that of the control animal. Ciliary activity in the tubotympanum showed no recovery through the observation period. On the other hand, intratympanic injection of 10(-6) M of histamine produced MEEs at 1 and 3 days postinjection when the mucociliary clearance time was longer than that of the control group. At 8 days, when most ears did not demonstrate MEEs, the mucociliary clearance time and ciliary activity in the Eustachian tube and tympanic orifice reached the level of the control group. Our present study demonstrates that histamine can induce mucociliary dysfunction of the tubotympanum resulting in middle ear effusions, and that cilia, especially those present in the tube and the tympanic orifice, have a significant role in eliminating middle ear effusions.
Insights
Histamine stimulates middle ear cilia via H2-receptors, but high concentrations impair function, leading to middle ear effusions (MEEs). Cilia in the Eustachian tube and tympanic orifice are crucial for clearing MEEs.
Area of Science:
- Otolaryngology
- Allergy and Immunology
- Cell Biology
Background:
- Histamine, a mediator in allergic and inflammatory responses, increases vascular permeability.
- Histamine presence in middle ear effusions (MEEs) suggests a role in their development and persistence.
- The impact of histamine on middle ear mucociliary function remains incompletely understood.
Purpose of the Study:
- To investigate the effect of histamine on mucociliary function in the middle ear.
- To determine the specific histamine receptors involved in modulating ciliary activity.
- To assess histamine's role in inducing and resolving middle ear effusions.
Main Methods:
- Examined the effect of various histamine concentrations (10(-8) M to 10(-2) M) on ciliary activity.
- Utilized H1 (diphenhydramine) and H2 (cimetidine) blockers to identify histamine receptor involvement.
- Administered intratympanic injections of histamine (10(-4) M and 10(-6) M) to induce MEEs in animal models.
- Monitored MEE volume, mucociliary clearance time, and ciliary activity post-injection.
Main Results:
- Histamine exhibited a biphasic effect: ciliostimulatory at 10(-8) M to 10(-4) M and inhibitory at 10(-2) M.
- Ciliostimulatory effects were mediated by H2-receptors, as evidenced by reduction with cimetidine but not diphenhydramine.
- Intratympanic histamine induced MEEs, with impaired mucociliary clearance and prolonged clearance times.
- Cilia in the Eustachian tube and tympanic orifice demonstrated a critical role in MEE resolution.
Conclusions:
- Histamine can induce mucociliary dysfunction in the tubotympanum, contributing to middle ear effusions.
- H2-receptor activation by histamine stimulates ciliary activity, while higher concentrations are detrimental.
- Efficient clearance of middle ear effusions relies significantly on the mucociliary function of the Eustachian tube and tympanic orifice.