Careers  |  Sign In  |  Register  |   Twitter

Montelukast in primary RSV ameliorates re-infections

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In mice, treating primary respiratory syncytial virus (RSV) with the cysteinyl leukotriene 1 receptor antagonist montelukast reduces airway hyperresponsiveness and inflammation after RSV re-infection, according to a May 4th online report in the American Journal of Respiratory and Critical Care Medicine.

“The drug is approved for infants, and I think a number of us have used the drug beginning in the fall and through the winter to try to prevent viral-induced exacerbations,” senior author Dr. Erwin W. Gelfand from National Jewish Health, Denver, Colorado, told Reuters Health by e-mail. “The drug is not approved for this indication at present.”

Hypothesizing that cysteinyl leukotrienes may play a critical role during primary RSV infection, especially in determining the airway response to subsequent RSV re-infection, Dr. Gelfand and colleagues investigated the effects of montelukast in newborn and adult mice with primary and secondary RSV infection.

With no treatment, cysteinyl leukotriene levels in bronchoalveolar fluid began rising on day 3 after primary infection. Airway hyperresponsiveness began to increase on day 5. The pattern of RSV-induced cysteinyl leukotriene release paralleled and appeared to precede the airway hyperresponsiveness.

Montelukast (30 mg/kg) significantly reduced airway hyperresponsiveness without altering baseline resistance, significantly reduced the number of lymphocytes in the bronchoalveolar fluid, and significantly increased the levels of interferon-gamma in the bronchoalveolar fluid.

Rates of viral replication and clearance did not differ between neonatal and adult mice or between montelukast-treated and control mice.

Treatment of primary RSV infection also prevented enhancement of airway hyperresponsiveness during re-infection, and reduced the number of total cells and eosinophils in the bronchoalveolar fluid and goblet cell metaplasia. Control mice showed none of these effects.

In contrast to primary infection, in re-infection the montelukast-treated mice had decreased levels of cysteinyl leukotriene and a reduced number of total cells in the bronchoalveolar fluid.

When the researchers treated mice with montelukast only during the secondary infection, it had no effect on re-infection responses.

“RSV and other viruses initially attack airway epithelium which initiates an inflammatory cascade involving different components of the immune system,” Dr. Gelfand said. “Currently, we are attempting to determine on which cell type the drug is blocking activation.”

“Asthma is a complex syndrome where in terms of drug therapy, one size does not fit all,” he added. “Considering which trigger exacerbates asthma in an individual is important, and we must consider individualizing therapy for each patient.”

Reference:
Am J Resp Crit Care Med 2010.