NATURAL AND EXPERIMENTAL RHINOVIRUS INFECTIONS OF THE LOWER RESPIRATORY-TRACT

Rhinoviruses are the cause of the majority of common colds, but their role in lower respiratory disorders is less clear. Recent studies using the polymerase chain reaction to detect rhinoviruses have established respiratory viral infections as major factors in the induction of acute exacerbations of asthma in both adults and children, both in mild exacerbations and in more severe exacerbations leading to hospital admission. Rhinoviruses were the major virus type detected in these studies, accounting for two-thirds of viruses detected. It is not known whether rhinoviruses produce their effects by directly invading the lower airway or by indirect means. Previous clinical studies provide some evidence that rhinoviruses are capable of infecting the lower airway. However, the immunologic response, both in the upper and lower airways, remains poorly defined. Recent studies have provided evidence of increased cellular activation in peripheral blood and in bronchial biopsies in atopic subjects compared with normal subjects during experimental rhinovirus infections. The reasons for these different cellular responses are unclear. Rhinoviruses as well as other respiratory viruses have been shown to increase levels of a variety of cytokines from respiratory epithelium, monocytes, or macrophages. Prominent among these cytokines is interleukin (IL)-8. We have detected increased levels of IL-8 in nasal secretions from subjects with wild-type rhinovirus infections. We studied the mechanisms of rhinovirus-induced IL-8 production and found protein release from both pulmonary epithelial and peripheral blood mononuclear cells. This protein production was accompanied by increased mRNA expression and evidence of infection of both pulmonary epithelial and monocyte cell lines. Finally, we demonstrated increased IL-8 promoter activity after rhinovirus infection. These studies suggest that rhinoviruses are indeed capable of infecting the lower airway and that they produce marked inflammatory responses when they do. This inflammatory response may be brought about in part by rhinovirus-induced activation of cytokine promoters.