Influence of infection on exacerbations of multiple sclerosis.

Exacerbations of multiple sclerosis (MS) are triggered by exogenous events, the best documented being viral upper respiratory infections (URIs), which can stimulate secretion of cytokines such as interferon-gamma (IFN-gamma) by immune cells. In conjunction with a recent clinical trial of systemic interferon-beta (IFN-beta) in relapsing-remitting MS, we studied the occurrence of viral infections and their correlation with MS attacks. Thirty patients kept daily logs, noting URI symptoms in themselves, family members, and co-workers. Patients were examined every 3 months, or whenever an attack of MS occurred, and were tested for antibodies to common upper respiratory pathogens. A strong correlation was found between MS attacks and URIs. There were 168 URIs in 2,792 patient-weeks, including 996 weeks at risk (the interval beginning 1 week before and ending 5 weeks after onset of URI symptoms) and 1,796 weeks not at risk. Nearly two-thirds of attacks occurred in periods at risk. Attack rates were 2.92 per year in weeks at risk compared to 1.16 per year in weeks not at risk, a significant difference (p < 0.001). High-dose interferon reduced the frequency of MS attacks, but had no effect on the number of URIs. Although a specific virus could not be incriminated, we concluded that URIs of presumed viral origin are an important trigger of MS attacks, and that treatment with IFN-beta reduces the attack rate, but not by preventing URIs. Rather, it may modulate responses to viral infection that would otherwise lead to immune activation and clinical symptoms.