Cyclosporine A reduces T lymphocyte activity and improves airway hyperresponsiveness in corticosteroid-dependent chronic severe asthma.
BACKGROUND
Although cyclosporine A is proving effective for chronic severe asthma, its mechanism of action in this disease is unclear.


OBJECTIVE
This open study was conducted to determine whether cyclosporine A therapy would reduce the degree of airway hyperresponsiveness and T lymphocyte activity.


METHODS
After a 6-week run-in period, nine patients with corticosteroid-dependent chronic severe asthma were treated with cyclosporine A (initial dose 5 mg/kg per day) for 12 weeks.


RESULTS
Weekly mean morning peak expiratory flow significantly increased in six subjects during the last 6 weeks of trial. Geographic mean PC20-acetylcholine (the provocative concentration of acetylcholine required to cause a 20% fall in FEV1) was 0.147 mg/mL before cyclosporine A treatment and increased to 0.216 mg/mL at 6 weeks and to 0.379 mg/mL at 12 weeks after treatment. The increase at 12 weeks was statistically significant (P < .05). The percentage of CD4-positive T lymphocytes bearing IL-2 receptor (a marker of T cell activation) in the peripheral blood decreased significantly at 6 weeks (P < .05), but returned to baseline value at 12 weeks, probably due to cyclosporine A dose reduction in seven subjects. Serum IgE levels and peripheral blood eosinophil counts, however, which are dependent on IL-4 and IL-5, respectively, were still significantly decreased at 12 weeks, suggesting lymphokine production remained suppressed even after cyclosporine A dose was reduced.


CONCLUSIONS
Taken together, these data suggest that cyclosporine A may act in asthma, at least in part, by inhibition of T lymphocyte activation and by reducing the degree of airway hyperresponsiveness.
Fukuda
T
T
Department of Internal Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan.
Asakawa
J
J
Motojima
S
S
Makino
S
S
D000305:Adrenal Cortex Hormones / Q000378:metabolism / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002908:Chronic Disease; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000305:Adrenal Cortex Hormones; D016572:Cyclosporine