Pharmacologic modulation of spontaneous histamine release

Area of Science:

• Immunology
• Pharmacology
• Respiratory Medicine

Background:

• Asthma is characterized by elevated spontaneous histamine release (SHR) from basophils in patients not on medication compared to those on chronic medication or normal subjects.
• Previous in vitro studies demonstrated that theophylline significantly inhibits SHR, with isoproterenol and PGE1 showing lesser effects.

Purpose of the Study:

• To investigate the in vivo effect of a single oral dose of bronchodilators on in vitro spontaneous histamine release (SHR) in asthmatic patients.
• To assess the impact of oral theophylline and metaproterenol on pulmonary function and SHR.

Main Methods:

• Eight asthmatic subjects with varying levels of SHR were studied on separate days.
• Pulmonary function and in vitro SHR were measured before and after administration of a single oral dose of theophylline (250 mg) or metaproterenol (20 mg).
• Baseline SHR levels were assessed for reproducibility.

Main Results:

• A significant correlation (r = .82) was observed in baseline SHR values between study days for the same individuals.
• Both theophylline and metaproterenol significantly improved pulmonary function.
• Neither theophylline nor metaproterenol administration affected the in vitro spontaneous histamine release (SHR) from basophils of asthmatic subjects.

Conclusions:

• While spontaneous histamine release (SHR) is a feature of asthma, it is not modulated by a single therapeutic dose of common oral bronchodilators.
• The in vitro inhibitory effects of theophylline on SHR do not translate to in vivo modulation after a single oral dose in asthmatic patients.
• Further research may be needed to explore other therapeutic strategies or dosages for managing SHR in asthma.