THE IN-VIVO EFFECT OF THEOPHYLLINE ON HISTAMINE RELEASE FROM HUMAN LEUKOCYTES

Abstract

The antigen-induced release of mediators from sensitized cells is an active secretory process, inhibited by drugs such as theophylline, which increase intracellular cyclic adenosine monophosphate concentration. This inhibition has been demonstrated in several in-vitro systems, but at concentrations (≥ 18μg/ml) which might not be achieved in vivo with the dosage commonly employed in treatment of asthma. This study investigated the possibility that theophylline, as commonly used for asthma therapy, might also inhibit mediator release. 7 atopic subjects (6 asthmatic children and an adult with hayfever) had leukocyte histamine release determined with an tigens to which they were sensitive. Release was measured at 8 a.m. and 12 noon on 2 control days and on a drug day, on which theophylline 6mg/kg was given orally at 8 a.m. Plasma theophylline levels were determined on each specimen of blood drawn for histamine release. 3 subjects had up to 38% inhibition of histamine release by theophylline; the other 4 patients showed no effect. 2 of the 3 subjects who showed inhibition had plasma theophylline levels in excess of 10μg/ml; all of the unresponsive subjects had levels less than 10μg/ml. The plasma level achieved by a given dose of theophylline is extremely variable among patients, but in some patients levels are achieved which will inhibit mediator release. This suggests that in some asthmatic children theophylline may have beneficial effects other than bronchodilatation.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD