Purpose: Inhaled corticosteroids (ICS) improve symptoms in lung diseases, such as asthma. Initial data suggest that the effects of ICS remain localized in the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We sought to evaluate the effect of ICS on peripheral immune mediators and hypothalamic-pituitary-adrenal axis and their response to exercise in healthy men.
Methods: Eleven healthy males (18-30 yr old) were placed on 2 wk of fluticasone proprionate (440 μg) twice daily. A 30-min bout of exercise was performed on a cycle ergometer at approximately 70% of peak work rate before and after the start of ICS. Blood was sampled before and after exercise. Cytokines and hypothalamic-pituitary-adrenal axis mediators were measured by ELISA, and fluticasone was measured by liquid chromatography/tandem mass spectrometry.
Results: After ICS treatment, cortisol and adrenocorticotropin were decreased, and a blunted exercise response was observed for cortisol, adrenocorticotropin, and growth hormone. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and the ICS-treated conditions and at baseline after ICS treatment. Interleukin-6 was elevated with ICS treatment, but the exercise response was blunted. Circulating median fluticasone levels were 0.15 ng·mL−1 and were increased to 0.20 ng·mL−1 in response to exercise.
Conclusions: Exercise revealed deficits in growth hormone production after ICS treatment not identified by static markers. Neutrophils were shown to be surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess the physiological effect of exogenous corticosteroids.
1Institute for Clinical and Translational Science, University of California - Irvine, Irvine, CA; and 2Child Health & Sports Center, Pediatric Department, Meir Medical Center, Sackler School of Medicine, Tel-Aviv University, ISRAEL
Address for correspondence: Dan M. Cooper, M.D., Pediatric Exercise Research Center, Department of Pediatrics, Bldg. 25, 2nd Floor, 101 The City Dr., Orange, CA 92868; E-mail: firstname.lastname@example.org.
Submitted for publication January 2010.
Accepted for publication March 2010.