The host response, not the virus, causes the symptoms of the common cold.

Viral colds remain common. For over 30 years, since sensisymptoms. These increases did not occur in volunteers who tive tissue-cell cultures came into use, rhinoviruses have been were infected but not ill. The presence of serum albumin was known to be the etiologic agent in at least one-third of colds thought to be indicative of a vascular leak in submucosal vesin adults. Detection of rhinoviral nucleic acid in respiratory sels. secretions by reverse transcription–PCR may increase substanTurner [8] began to explore the means by which rhinovirus tially the number of colds to which we can assign a rhinoviral infection of a small number of cells could result in an influx etiology [1]. Although at least partial immunity to reinfection of PMNs into the mucosa and nasal secretions. He demonis provided by rhinovirus infection, the multiplicity of serotypes strated that fibroblasts in cell culture elaborated a chemoattrachas made development of a vaccine an unattractive prospect. tant for PMNs in response to infection with rhinovirus. The The article by Turner and colleagues [2] is part of an ongoing chemoattractant proved to be IL-8 [9]. investigation of the pathogenesis of symptoms in rhinovirus The concept that individual epithelial cells elaborate cytocolds. The focus of this investigation is the mechanism(s) by kines and chemokines in response to infection with one of the which rhinovirus infection of epithelial cells in the upper airrespiratory viruses has been supported by the work of several ways causes the symptoms of rhinorrhea, nasal obstruction, investigators [10–12]. Elevated levels of cytokines, including sore/scratchy throat, and cough that we all know as a cold. The IL-1b, IL-6, and IL-8, have been found in nasal secretions original concept was that symptoms resulted from destruction during colds [13, 14]. Thus it appears that a small number of of nasal epithelium. However, this concept was shown to be cells infected with virus elaborate a variety of cytokines to wrong by Winther et al. [3], who examined the nasal epithelium initiate an inflammatory cascade. in biopsy specimens from people with natural colds. They The viral infection per se does not produce symptoms; rather, found that epithelium was intact and that the only distinguishit is the host response to the viral infection that is responsible ing feature of biopsy specimens during the cold was an infor the symptoms. Indeed, Turner and co-workers [2] demoncreased number of polymorphonuclear neutrophils (PMNs) in strated that inoculation of virus into the nose of susceptible the submucosa and epithelium. volunteers was followed either by infection (viral replication) with no increase in IL-8 and no symptoms or by infection with See the article by Turner et al. on pages 840–6. release of IL-8 and appearance of symptomatic illness. Our current concept of the pathogenesis of symptoms in rhinovirus infection suggests two different lines of attack for Turner and co-workers [4] also reported that there was minireducing the misery of colds: (1) attack the virus with antiviral mal tissue loss during rhinovirus colds. Recently, Bardin et al. agents or (2) attempt to block or dampen the host response. [5] and Arruda et al. [6] used in situ hybridization to demonThe trial of pentoxifylline in rhinovirus infection by Turner et strate that rhinovirus replication was occurring in an extremely al. [2] was an attempt to interrupt the host response. Although small number of cells in nasal epithelial biopsy specimens from the pentoxifylline as employed in this study had no effect, volunteers infected with rhinovirus. Because of the lack of alteration of the inflammatory cascade in the nose without morphological damage to the epithelium of the nose during attacking the virus is an attractive approach. It may be that rhinovirus infection, Turner and co-workers [4] hypothesized this approach would allow the host to become immune to the that symptoms resulted from an inflammatory cascade triggered infecting serotype of rhinovirus without the usual accompaby the viral infection by an unspecified mechanism. nying symptomatic illness. The work of Naclerio and co-workers [7] supported the inThe migration of PMNs into the nose and nasal secretions flammatory-cascade hypothesis. They analyzed nasal washings in rhinovirus colds is due, at least in part, to the elaboration obtained every 4 hours from volunteers following inoculation of IL-8 by infected epithelial cells. That the host response to with rhinovirus. They found PMNs, serum albumin, and kinins uncomplicated viral infection causes an increase in PMNs in increased in nasal washings of infected volunteers who develnasal secretions is an important fact for clinicians to know, oped symptoms, and the increases paralleled the occurrence of because the PMNs may add color to the nasal discharge. The color of nasal secretions is often taken by patients and doctors alike as an indication of whether bacterial superinfection has Received 24 November 1997. occurred during a viral upper respiratory tract infection. UnforReprints or correspondence: Dr. J. Owen Hendley, Pediatric Infectious Diseases, Box 386, University of Virginia Health Sciences Center, Charlottesville, tunately, it is not that easy. Virginia 22908. Winther and co-workers [15] found that one-half of medical Clinical Infectious Diseases 1998;26:847–8 students with uncomplicated colds reported colored discharge q 1998 by The University of Chicago. All rights reserved. 1058–4838/98/2604–0005$03.00 by day 3–5 of illness. The 100-fold increase in PMNs in rhino-