Minimal dose of aerosolized interferon-alpha in human subjects: biological consequences and side-effects.
Interferon-alpha (IFN-alpha) is a leucocyte-derived cytokine 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 lymphoblastoid IFN-alpha, in normal subjects and patients with chronic bronchitis, using serum 2'-5' oligoadenylate synthetase (OAS) as a marker of IFN-alpha activity. 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-alpha dose able to induce biological effects without side-effects. IFN-alpha was given in a dose escalation trial including 0, 0.3 x 10(6), 1.0 x 10(6) and 3.0 x 10(6) IU.day-1 (5 day administration). Only the administration of 3.0 x 10(6) IU.day-1 of IFN-alpha 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 10(6) 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-alpha levels was found. It is concluded that aerosolized IFN-alpha 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.
Giosuè
S
S
Dipartimento di Scienze Cardiovascolari e Respiratorie, Università La Sapienza, Rome, Italy.
Casarini
M
M
Ameglio
F
F
Alemanno
L
L
Saltini
C
C
Bisetti
A
A
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000097:blood; D000280:Administration, Inhalation; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D001991:Bronchitis / Q000378:metabolism / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D001613:beta 2-Microglobulin / Q000032:analysis
D016898:Interferon-alpha; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D015088:2',5'-Oligoadenylate Synthetase