DESENSITIZATION OF THE ADENYLYL-CYCLASE SYSTEM IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS WITH ASTHMA 3 HOURS AFTER ALLERGEN CHALLENGE

Background: Bronchial hyperreactivity is a common characteristic of pa tients with asthma and is often associated with enhanced activities of peripheral blood cells. Signal transduction systems are important in regulating cellular activities and can be modified by allergen challen ge. Methods: Patients with allergic asthma (n = 15) were challenged wi th house dust mite allergen, resulting in an asthmatic response. Adeny lyl cyclase activity was measured in membranes from peripheral blood m ononuclear cells before, 3 hours after, and 24 hours after challenge. Results: Allergen challenge proved to have opposite effects in two dis tinct subgroups of patients. In 10 patients (group I) a heterologous d esensitization of the adenylyl cyclase system was observed after chall enge, whereas in five patients (group II) an increase in adenylyl cycl ase activity was found. Adenylyl cyclase activity before allergen chal lenge in group II was significantly lower than in group I and comparab le to cyclase activity found in group I after allergen challenge. This suggests that in these five patients the adenylyl cyclase system was already desensitized before the start of the study, possibly as a resu lt of natural allergen exposure. Heterologous desensitization in group I was found within 3 hours after allergen challenge, that is before t he onset of the late bronchoconstrictive reaction. Conclusions: Becaus e adenylyl cyclase is important in the regulation of cytokine producti on by mononuclear cells, alteration of cytokine production induced by desensitization of adenylyl cyclase could therefore play a role in the development of the late bronchoconstrictive reaction.