title: Intranasal tolerance and histopathologic effects of a novel synthetic interferon, rIFN-alpha Con1.
abstract: In a double-blind trial 119 adults were randomly assigned to receive daily sprays of placebo (N = 30) or rIFN-alpha Con1 3 MU (N = 29), 9 MU (N = 30), or 30 MU (N = 30) per day for 25 consecutive days. Fifty-nine subjects were removed from treatment because of abnormal nasal exams (N = 56) or irritative symptoms (N = 3). The fraction of drop-outs in the placebo group (30%) was significantly different (P less than 0.05) from that in the 3 MU (55%), 9 MU (57%), or 30 MU (67%) groups. Nasal mucosal biopsies collected 1-2 days after completing spray use detected moderate or marked lymphocytic infiltration in 10% of placebo (N = 10), 90% of 3 MU (N = 9), 85% of 9 MU (N = 13), and 70% of 30 MU (N = 10) subjects (P less than 0.05, placebo vs each rIFN-alpha Con1 group). All 3 dose levels of rIFN-alpha Con1 were associated with significant clinical and histopathologic signs of nasal irritation. The findings suggest that intranasal rIFN-alpha Con1 does not have a more favorable therapeutic index than rIFN-alpha 2 and that the risk of nasal irritation relates more closely to the anti-viral activity than the protein content of the rIFN-alpha administered.
authors.affiliation: Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
authors.forename: F G
authors.initials: FG
authors.lastname: Hayden
authors.forename: D J
authors.initials: DJ
authors.lastname: Innes
authors.forename: S E
authors.initials: SE
authors.lastname: Mills
authors.forename: P A
authors.initials: PA
authors.lastname: Levine
mesh_terms: D000328:Adult; D000336:Aerosols; D001706:Biopsy; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009296:Nasal Cavity / Q000187:drug effects* / Q000473:pathology; D010850:Picornaviridae Infections / Q000517:prevention & control*; D011897:Random Allocation; D011994:Recombinant Proteins; D012141:Respiratory Tract Infections / Q000517:prevention & control*; D012229:Rhinovirus
chemical_list: D000336:Aerosols; D007370:Interferon Type I; D011994:Recombinant Proteins