Intranasally Applied Recombinant Leukocyte A Interferon in Normal Volunteers. II. Determination of Minimal Effective and Tolerable Dose

Abstract

In an attempt to find a dose of recombinant leukocyte A interferon (rIFN-alpha A) that is both efficacious against rhinovirus challenge and is tolerable, double-blind, placebo-controlled studies were performed; 56 normal volunteers received either placebo or one of two relatively small doses of rIFN-alpha A (i.e., 2.4 X 10(6) units [2.4M] or 0.7 X 10(6) units [0.7M] per day) for four days. The frequency of illness was significantly lower in the group given doses of 2.4M than in a group of volunteers given placebo (29% vs. 73%; P less than .032); however, the frequencies of illness in the group given doses of 0.7M and in a placebo group were similar (67% vs. 63%). The rates of infection in these pairs of groups were not significantly different from each other. No significant local or systemic reactions were noted during the four days of rIFN-alpha A administration. In a 26-day tolerance study, 15% of volunteers given 2.4M doses of rIFN-alpha A developed bloody mucus and nasal mucosal erosions, while no such local reactions were noted in volunteers given 0.7M doses or in those given placebo. Thus, increasing doses of rIFN-alpha A were associated with both increasing efficacy against rhinovirus-induced illness and increasing frequency of local adverse reactions.

Demonstration of dose-response relationship in seasonal prophylaxis of respiratory infections with alpha-2b interferon

“…Progressively lower doses have been examined in experimental studies to find a prophylactic window, that is, a regimen which would have acceptable efficacy without unacceptable side effects. The challenge studies were carried out for short periods, but the investigators involved felt that the side effects they observed in using the same doses for periods of 26 days without viral infection paralleled in magnitude the prophylactic effect they had documented (15,16).…”

Contrasting effects of type I interferon as a mucosal adjuvant for influenza vaccine in mice and humans

“…We used dosages of 1 to 10 Mu daily in our rhinovirus studies in humans but dosages as high as 40 Mu per day were used (23). Rhinorrhea, sometimes blood-tinged, appeared in those studies but only when higher dosages were continued for several days (21-22). In the present study, there was no significant increase in local reactions but a significant increase in systemic complaints occurred for the 10 Mu dosage for combined moderate and severe reaction frequencies.…”

A randomized controlled trial of low-dose recombinant human interferons α-2b nasal spray to prevent acute viral respiratory infections in military recruits

“…The previous studies have suggested that high dosage of intranasal interferons can prevent respiratory infections caused by viruses, such as influenza virus, rhinovirus, coronavirus and respiratory syncytial virus [10][11][12][13][14]. However, the major problem is higher frequency of local side effects such as mucosal irritation, dry mucous membranes, blood-tinged mucus and nasal mucosal erosion [15][16][17]. Recently, YUANCE Medicine Company (Beijing, China) has developed a low-dose recombinant human interferon ␣-2b (rIFN␣-2b) nasal spray in order to reduce adverse reactions.…”