Minimal dose of aerosolized interferon-α in human subjects: Biological consequences and side-effects

Abstract

Interferon-α (IFN-α) is a leucocyte-derived cytokiue with pleiotropic effects on the cells of the immune system, including the ability to promote viral and microbial killing. This study was designed to evaluate the biologically active dosage of aerosolized Iymphoblastoid IFN-α, in normal subjects and patients with chronic bronchitis, using serum 2'-5' oligoadenylate synthetase (OAS) as a marker of IFN-α actitivity. Three groups of subjects were included: two healthy groups and one of patients with chronic bronchitis. Group A (controls, n = 5) was studied in order to determine the minimal IFN-α dose able to induce biological effects without side-effects. IFN-α was given un a dose escalation trial including 0, 0.3 x 106, 1.0 x 106 and 3.0 x 106 IU·day-1 (5 day administration). Only the administration of 3.0 x 106 IU·day-1 of IFN-α induced a significant biological activity, increasing serum levels of OAS. Group B (controls, n = 5) and C (chronic bronchitis, n = 5) were given 3.0 x 106 IU day-1 (10 day administration) in order to study serum, bronchoalveolar lavage fluid (BALF) and BALF cell modifications, after treatment. OAS serum levels and nitroblue tetrazolium (NBT) reduction tests, the latter used as a measure of phagocyte cell activity, increased both in normal subjects and in patients with chronic bronchitis. No significant change of serum IFN-α levels was found. It is concluded that aerosolized IFN-α administration to the lung is well-tolerated at biologically active doses. The activity can be monitored by quantifying OAS serum levels through a simple blood test.