Effects of high-dose inhaled fluticasone propionate via spacer on cell-mediated immunity in healthy volunteers

Background: Systemic corticosteroids are known to alter cell-mediated immun ity (CMI); However, the effects of inhaled steroids on CMI are unclear. We therefore sought to assess CMI following high-dose inhaled steroids in heal thy subjects. Methods: Ten healthy nonasthmatic subjects self-administered fluticasone pr opionate (FP), 440 mug bid, with a spacer device. CMI was assessed by delay ed hypersensitivity skill testing to multiple antigens and in vitro by phyt ohemagglutinin (PHA) stimulation of peripheral blood T lymphocytes. Percent ages of CD3(+) CD4(+), and CD3(+)CD8(+) cells expressing CD69(+) were deter mined by three-color flow cytometry. Studies were conducted before and afte r 4 weeks of FP treatment. Results: After 4 weeks of FP treatment, two of nine subjects became anergic , whereas six of nine subjects had reduced skin responses (one subject was excluded). Mean total skin test score fell from 18.4 +/- 10.9 to 9.1 +/- 7. 2 mm (p = 0.02). There was a decline in tuberculin responses in all four su bjects who were positive prior to FP treatment. Following FP treatment, the percentage of unstimulated (from control subjects receiving saline solutio n) CD3(+)CD4(+)CD69(+) cells declined from 14.8 +/- 4.2% to 8.5 +/- 4.6% (p = 0.02) and the CD3(+)CD8(+)D69(+) cells decreased from 29.7 +/- 12.7% to 17.1 +/- 5.0% (p = 0.007). PHA stimulation produced significant increases i n the percentage of CD3(+)CD4(+)CD69(+) cells before and after FP treatment (67.0 +/- 9.1%, p < 0.02 before FP; 55.4 +/- 17.0%, p < 0.02 after FP), an d in the percentage of CD3(+)CD8(+)CB69(+) cells before and after treatment (79.7 +/- 9.3%, p < 0.03 before FP; 71.2 +/- 11.4%, p = 0.008 after FP). Conclusions: High doses of FP suppress the proportion of activated circulat ing T cells but do not affect the ability of T cells to respond to direct s timulation with PHA. However, depression of skin test responses to antigens following treatment with FP suggests an impairment of in vivo clinical man ifestations of T-cell, activation by a mechanism that requires further inve stigation.