Human tolerance and histopathologic effects of long-term administration of intranasal interferon-alpha 2

Fifty-two healthy adults were randomly assigned interferon-alpha 2 (HuIFN-alpha 2), 8.4 X 10(6) U/day, or placebo by intranasal spray for 28 days. Symptoms, nasal examinations, and histologic analysis of nasal biopsy specimens obtained three days before and one day after exposure were evaluated under blind conditions. HuIFN-alpha 2 was associated with signs of mucosal irritation (dry mucous membranes, crusts, and friability) and/or symptoms (blood-tinged mucus) in 23% of recipients. Moderate or marked epithelial acute inflammation with ulceration occurred in 19% of HuIFN-alpha 2 recipients. Pronounced submucosal lymphocytic and mononuclear cell infiltrates developed in 58%. These histopathologic abnormalities resolved within eight weeks of stopping exposure. These results indicate that long-term or indefinite intranasal administration of HuIFN-alpha 2 at the dosages used in this study is not feasible strategy for prophylaxis of respiratory viral infections.