Background: 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.
Methods: Ten healthy nonasthmatic subjects
self-administered fluticasone propionate (FP), 440 μg 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.
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 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.