Glucocorticosteroid therapy in asthma modulates the expression of histamine receptors mRNA in peripheral lymphocytes

Abstract

Among a numerous pathophysiological influences, histamine modulates an immunological response through stimulation of an appropriate receptor. It acts proinflammatory through H1R and immunosuppressively through H2R. During wheezing in asthma, the concentration of histamine in blood is considerably increased. Glucocorticosteroids (GCS) are the most efficient drugs in the therapy of asthma due to their potent anti-inflammatory and immunosuppressive activity.
We investigated the expression of four histamine receptors mRNA in peripheral lymphocytes of 7 healthy subjects, 8 asymptomatic (untreated) and 14 GCS-treated asthmatics (12.0±2.5 mg/daily). The study was performed on isolated lymphocytes using RT-PCR technique. Primers were labelled with fluorescent dyes. Data were analysed using ABI Prism sequencer and Gene Scan collection software, version 3.1. Intensity of fluorescence was expressed in relative fluorescence units.
It was found that the expression of H1 and H4 mRNA did not differ between the groups in contrast to H2R mRNA expression, which was significantly lower in untreated asthmatics than in control (p<0.01). In treated asthmatics this expression was similar to those in healthy subjects and significantly higher than in untreated asthmatics (p<0.001). Expression of H3R mRNA was similar in healthy and untreated subjects whereas significantly higher in treated patients (p<0.02). An increase in expression of H2R mRNA may be an important element in the mechanism of action of GCS considering documented participation of histamine, through H2R, in suppression of immunological response.