Effects of High-Dose Inhaled Fluticasone Propionate via Spacer on Cell-Mediated Immunity in Healthy Volunteers

Abstract

Systemic corticosteroids are known to alter cell-mediated immunity (CMI). However, the effects of inhaled steroids on CMI are unclear. We therefore sought to assess CMI following high-dose inhaled steroids in healthy subjects. Ten healthy nonasthmatic subjects self-administered fluticasone propionate (FP), 440 microg bid, with a spacer device. CMI was assessed by delayed hypersensitivity skin testing to multiple antigens and in vitro by phytohemagglutinin (PHA) stimulation of peripheral blood T lymphocytes. Percentages of CD3(+), CD4(+), and CD3(+)CD8(+) cells expressing CD69(+) were determined by three-color flow cytometry. Studies were conducted before and after 4 weeks of FP treatment. 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 subjects who were positive prior to FP treatment. Following FP treatment, the percentage of unstimulated (from control subjects receiving saline solution) CD3(+)CD4(+)CD69(+) cells declined from 14.8+/-4.2% to 8. 5+/-4.6% (p = 0.02) and the CD3(+)CD8(+)CD69(+) cells decreased from 29.7+/-12.7% to 17.1 +/-5.0% (p = 0.007). PHA stimulation produced significant increases in 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), and in the percentage of CD3(+)CD8(+)CD69(+) cells before and after treatment (79.7+/-9.3%, p<0.03 before FP; 71.2+/-11.4%, p = 0. 008 after FP). High doses of FP suppress the proportion of activated circulating T cells but do not affect the ability of T cells to respond to direct stimulation with PHA. However, depression of skin test responses to antigens following treatment with FP suggests an impairment of in vivo clinical manifestations of T-cell activation by a mechanism that requires further investigation.