Seasonal variations in cyclic AMP production by peripheral blood mononuclear cells in allergic asthmatics.

BACKGROUND: Dysfunction of the beta-adrenoceptor (betaAR)/adenylyl cyclase (AC) system can impair the response of different cell types, including lymphocytes. In asthma, impairment of this system as well as changes in cytokine production by lymphocytes have been described. Because the severity of asthma can change over the year, a circannual pattern of the betaAR/AC system activity may also exist. OBJECTIVES: We set out to examine the activity of this betaAR/AC signal transduction system in peripheral blood mononuclear cells (PBMCs) of allergic asthmatics to asses whether differences existed between seasons. We investigated whether changes were associated with asthma severity and circannual changes in serum cortisol levels. METHODS: During 19 months, 41 allergic asthmatics (mean age 28 years) with nocturnal airway obstruction were enrolled in the study. AC activity was measured by cyclic AMP production. Resting, stimulated and potentiated AC activities and their relationships with clinical parameters, seasonal influences and serum cortisol levels were assessed. RESULTS: The AC activity in resting, stimulated and potentiated cells varied during the year. AC activity was relatively low in the periods June-August and September-November, and higher in December-February and March-May. Receptor-mediated and potentiated responses expressed as percentage of the resting response were equivalent throughout the year. Serum cortisol levels were positively related to AC activity. No relationships were found between clinical parameters and AC activity or serum cortisol levels. CONCLUSIONS: These results indicate that AC activity in PBMCs of allergic asthmatics shows a seasonal variation. However, seasonal differences in AC activity seems to be unrelated with clinical parameters. Other factors such as serum cortisol levels may have a modulating influence on AC activity. Future studies of AC systems in blood cells of asthmatic patients need to take into account these seasonal influences.

Dextran sedimentation induces a difference in the percentage of hypodense eosinophils in peripheral blood between children with allergic asthma and healthy controls.

Considerable differences in the percentage of hypodense eosinophils in the peripheral blood of asthmatics have been reported by different investigators. In these previous studies dextran sedimentation was used for removal of erythrocytes prior to density centrifugation. We hypothesized that the sedimentation procedure might induce the presence of hypodense eosinophils in the peripheral blood of asthmatic patients. In order to test this hypothesis, we compared eosinophil density profiles from peripheral blood of children with asthma and of age-matched healthy controls, using different procedures. In the first method (direct method) blood samples were directly layered on a discontinuous Percoll gradient. Erythrocytes were removed by isotonic lysis. In the second method (dextran sedimentation) erythrocytes were removed by sedimentation with dextran prior to gradient centrifugation. Results of the direct method show no significant difference in percentage of hypodense eosinophils between children with asthma and healthy controls (9.19% and 6.84% respectively). However, after dextran sedimentation, children with asthma had a significantly higher percentage of hypodense eosinophils than healthy controls (15.40% and 8.84% respectively; P < 0.05). The percentage of hypodense eosinophils was correlated with the number of eosinophils and with the lung function, measured as the Tiffeneau index (FEV1/VC), in the whole group of subjects when the direct method was used. We conclude that an increased percentage of hypodense eosinophils is not present in the circulation of children with asthma, but can be induced in vitro by dextran sedimentation. Therefore, in vitro generation of hypodense eosinophils in the blood of patients with asthma seems to be related with the primed state of eosinophils.

Allergen-induced changes in adenosine 5'-monophosphate bronchial responsiveness: effect of nedocromil sodium.

Bronchial hyperresponsiveness to adenosine 5'-monophosphate (AMP) was studied after allergen challenge in allergic asthmatic patients. Measurements were made with and without nedocromil sodium pretreatment. Nedocromil sodium inhibited both the early and late asthmatic reactions (P < .01). After allergen challenge a significant decrease in PC20 AMP from 12.2 mg/mL to 4.47 mg/mL (P < .05) at three hours was found, returning almost to baseline values: 10.85 mg/mL (P > .05) at 24 hours. Nedocromil sodium, 6 mg, given before allergen challenge prevented the increased responsiveness to AMP at three hours [PC20 10.12 mg/mL (P < .05)], but caused a decrease in PC20 AMP at 24 hours to 6.32 mg/mL (P < .05). Desensitization of the adenosine receptor during the late asthmatic reaction, which is prevented by nedocromil sodium, may explain the lack of increased responsiveness at 24 hours. AMP may play a physiologic role in allergen-induced late phase reactions.