Leukocyte Migration Inhibition in Propranolol-induced Pneumonitis: CASE REPORT
Clinical History and Findings
A 59-year-old man, formerly a smoker, complained of exertional dyspnea and was found to have interstitial pneumonitis. He had been receiving treatment with propranolol for 30 months, 40 mg per day (cumulative dose, 36 g). The roentgenogram showed small opacities disseminated over both lungs. A chest x-ray film taken three years earlier was normal. Cardiac volume was normal. All results of investigations for congestive heart failure were negative. Respiratory function tests showed a restrictive syndrome with hypoxia (Pa02=7.9 kPa) and a vital capacity reduced to 50 percent of the predicted value. All tests in sputum and serum for bacterial, viral and fungal infection were negative. No evidence of collagen vascular disease was found. Bronchoalveolar lavage showed lymphocytic alveolitis with 44.9 percent lymphocytes. Lymphocytosis fell to 19 percent nine weeks after the treatment was stopped but rose again to 28.6 percent after six weeks’ treatment was resumed, then fell again to 8.9 percent 15 weeks after treatment had finally been stopped. By this time dyspnea had disappeared and vital capacity had increased to 78 percent of the predicted value.
Leukocyte Migration Inhibition Test in Presence of Propranolol
This test was performed in the patient and in two subjects aged 50 and 59 years treated with propranolol for five and seven years, respectively, daily doses of drug being 60 and 240 mg and cumulative doses, 109 and 613 g, respectively. These two subjects were free from respiratory symptoms and their chest x-ray films and pulmonary function tests were normal (treated controls).
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In addition, a normal subject, taking no drugs, provided normal lymphocytes and granulocytes of peripheral blood.
Granulocytes and lymphocytes of each subject were obtained by centrifiigation of 20 ml of heparinized (50 U/ml) peripheral blood on Percoll gradients as described by Hjorth et al (1981).® After lysis of red cells in granulocyte suspensions by cold 0.83% NH4 CI, and washing, viable cells were counted, and the granulocytes mixed, or not, with the lymphocytes in the ratio of 2:1.
Four types of cell suspensions were prepared for migration as follows:
(1) The patients lymphocytes were mixed with granulocytes obtained from the normal subject.
(2) The patients granulocytes (one-half) were mixed with lymphocytes from the same normal subject as above.
(3) The other half of the patients granulocytes alone.
(4) Granulocytes of each of the two control subjects, treated with propranolol but without pneumonitis, were mixed with their own lymphocytes.
One microliter agarose microdroplets of each of these cell suspensions were made to migrate in presence, or not (control migrations), of concentrations of propranolol ranging from 10-8 through 10s до/ml (11 logs) in RPMI 1640 medium containing 20 mM HEPES buffer, 100 U/ml penicillin, 100 jig/ml streptomycin and 20 percent decomplemented FCS (medium). Leukocyte migra-tion from 12 (± 2) microdroplets was quantitated at 15, 36 and 60 hs of culture for each propranolol concentration and for each of the five cell suspensions with a photoelectric procedure previously described. Cell migration in medium containing propranolol was compared with migration of the same cells in medium without the drug for each of the cell suspensions and at each drug concentration used, the effect being expressed in percentage. generic cialis soft tabs
Results are expressed as mean ± standard error in the Table. Statistical comparisons were made using Students two-tailed t test.