CHARLOTTESVILLE, VA—A combination of intranasal interferon alfa-2b, oral chlorpheniramine, and oral ibuprofen initiated one day after experimental rhinovirus exposure reduced viral symptoms by 33% to 73% in a recent study.[1]

Intranasal application directs interferon to the site of rhinovirus replication, thereby maximizing antiviral action. Jack M. Gwaltney, Jr, MD, Professor of Internal Medicine at the University of Virginia Medical School, anticipates approval for intranasal interferon within a few years.

But antiviral therapy is not enough. “Infection triggers the release of inflammatory substances … such as histamines, kinins, prostaglandins, interleukins—it’s these things that actually cause the symptoms,” Dr. Gwaltney told PULMONARY REVIEWS. “If you just treat with interferon alone, you’re not doing anything to block these inflammatory pathways.” Colds, he argued, demand a “double approach: Get the virus, and get the mediators.”

Thus, Dr. Gwaltney and colleagues enlisted the over-the-counter antihistamine chlorpheniramine and the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen against rhinoviral symptoms. Antihistamines reduce sneezing and the need for nose-blowing, as well as the volume of nasal secretions in colds. Additionally, both antihistamines and NSAIDs are effective in reducing cough.

THREE DRUGS REDUCE COLD SYMPTOMS

This tripartite regimen was tested on 150 healthy subjects, ages 18 to 51. Each was nasally inoculated with rhinovirus a day before one of three treatments: three doses of intranasal interferon in the first two days, combined with ibuprofen (400 mg) and chlorpheniramine (12 mg) given every 12 hours for the next 4.5 days; ibuprofen and chlorpheniramine with nasal placebo; or both nasal and oral placebos. Sneezing, rhinorrhea, nasal obstruction, sore throat, cough, headache, malaise, and chills were scored (on a 0 to 4 scale) on the five mornings following inoculation, and nasal-wash viral titers were counted.

One day after treatment began, when symptoms in controls had peaked, full-regimen (but not partial-therapy) recipients were significantly less likely to have rhinorrhea, sneezing, or sore throat. After one day of treatment, placebo recipients who started with moderate symptoms had scores almost double those of subjects given triple therapy; this decrement in symptom severity broadened into a 3.34-fold difference after the fourth day. However, no such differences in symptoms were seen between the placebo recipients and those given partial therapy. On the second day of treatment, viral titers in placebo recipients measured 1.64-fold and 1.55-fold higher, respectively, than viral loads in patients given full or partial therapy.

TIMING IS ESSENTIAL

“Cold symptoms are the most prominent and there’s the biggest burden of illness in the first three days,” Dr. Gwaltney remarked. Optimally, therapy should be initiated when cold symptoms first appear. “If you don’t start early, you’re not going to get the major benefit of treatment,” he said. “You want to block those inflammatory pathways.” In this study, interferon treatment was limited to two days “because after 48 hours the virus growth starts to go down naturally,” Dr. Gwaltney explained. “If you use interferon in the nose over a prolonged period—say, a week or longer—then it starts to irritate the nose.”

—Mimi Zucker, PhD

Reference
1. Gwaltney JM Jr, Winther B, Patrie JT, Hendley JO. Combined antiviral-antimediator treatment for the common cold. J Infect Dis. 2002;186:147-154.

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