Tolerance and nasal histopathologic effects of long-term, low-dose intranasal recombinant interferon alpha-2A...

The dose-related tolerance and histopathologic effects of intranasal recombinant interferon alpha-2a (rIFN-alpha 2a) were determined in a blind study in which healthy subjects were randomized to receive sprays of interferon (IFN) (3 or 6 MU/day) or placebo for 28 days. Adverse nasal symptoms (bleeding, obstruction, irritation) tended to occur more often in the IFN 6 MU/day group. Blind analysis of biopsy samples collected before and after IFN treatment revealed that both IFN groups had significant histologic changes, most commonly an increased degree of lymphocytic infiltration in the subepithelium and underlying glandular zones. Changes developed in 61% of 18 recipients of IFN 6 MU/day, 37% of 19 recipients of IFN 3 MU/day, and 6% of 18 placebo recipients. Serum antibodies to rIFN-alpha 2a detectable by EIA were found in 4 recipients of IFN 3 MU/day and 2 recipients of IFN 6 MU/day, one-third of whom were positive by neutralization bioassay. The findings would predict that these rIFN-alpha 2a dosages would be associated with an excess of adverse side effects during long-term use in healthy adults.