Relationships among specific viral pathogens, virus-induced interleukin-8, and respiratory symptoms in infancy Respiratory viruses are important causes of illnessininfants.Theyarethemajorcauseofthe common cold and, in severe cases, can produce bronchiolitis and pneumonia. During an infec- tion,thecytopathiceffectsofvirusescontributeto thesymptomseveritybydestroyingtheepithelium lining the airways, which can lead to plugging of theairwaylumen,andexposureofnervereceptors that can trigger cough and neurogenic inflamma- tion(1).Inaddition,ithasbeenhypothesizedthat theimmuneresponsetoavirusalsocontributesto the severity of the illness. This may be especially important during infections with rhinoviruses (RV), which are thought to infect only a small subset of airway epithelial cells, and cause little cytopathology, even during severe colds (2, 3). Thishypothesisisalsosupportedbyobservations of experimentally induced RV infections, during which respiratory symptom scores correlate with recruitment and activation of leukocytes to the airway, as well as to levels of inflammatory mediatorsandcytokinesintheairway(4). Neutrophils are the principal cells recruited to the airway during viral respiratory infections (5, 6). There are suggestions from studies of experimentally induced and naturally acquired colds that neutrophils can contribute to the severity of both upper and lower respiratory Gern JE, Martin MS, Anklam KA, Shen K, Roberg KA, Carlson- Dakes KT, Adler K, Gilbertson-White S, Hamilton R, Shult PA, Kirk CJ, Da Silva DF, Sund SA, Kosorok MR, Lemanske Jr RF. Rela- tionship between specific viral pathogens, virus-induced interleukin-8, and respiratory symptoms in infancy. PediatrAllergyImmunol2002:13:386–393. Ó2002BlackwellMunksgaard Both virus-mediated damage to airway tissues and induction of pro- inflammatory cytokines such as interleukin-8 (IL-8) could contribute to symptom severity during viral respiratory infections in children. To test the hypothesis that IL-8 contributes to the pathogenesis of respiratory symptoms during naturally acquired respiratory viral infections in children, nasal wash samples collected from infants with acute viral infections (n ¼ 198) or from healthy uninfected infants (n ¼ 31) were analysed for IL-8. Nasal wash IL-8 was positively related to age in uninfected children (r s ¼ 0.36, p < 0.05). Respiratory syncytial virus (RSV) infection caused more severe respiratory symptoms compared to infections with influenza A, parainfluenza viruses, or rhinoviruses. In addition, RSV, parainfluenza and rhinovirus infections increased levels of IL-8 in nasal lavage fluid, and there were some differences in the ability of the viruses to induce IL-8 production (RSV>influenza, p < 0.05). Finally, there were significant correlations between nasal wash IL-8 levels and symptom scores during infections with rhinovirus (r s ¼ 0.56, p < 0.001)orinfluenzaA(r s ¼ 0.45, p < 0.05), but not with parainfluenza virus or RSV. These findings provide evidence of a close relationshipbetweenthegenerationofIL-8andsymptomsduringacute community-acquired infections with rhinovirus or influenza A. In contrast, for RSV and parainfluenza infections, factors in addition to IL-8 production appear to contribute to the generation of clinical symptoms. James E. Gern 1 , Matthew S. Martin 1 , Kelly A. Anklam 1 , Kunling Shen, Kathy A. Roberg 1 , Kirstin T. Carlson- Dakes 1 , Kiva Adler 1 , Stephanie Gilbertson-White 1 , Rebekah Hamilton 1 , Peter A. Shult 2 , Carol J. Kirk 2 , Douglas F. Da Silva 1 , Sarah A. Sund 1 , Michael R. Kosorok 3 and Robert F. Lemanske Jr 1,4 Departments of 1 Pediatrics, 4 Medicine, 2 Wisconsin State Laboratory of Hygiene and Preventive Medicine, and 3 Biostatistics & Medical Informatics, University of Wisconsin-Madison, WI, USA Key words: rhinovirus; respiratory syncytial virus; parainfluenza virus; influenza A; children; interleukin-8 Correspondence: James E. Gern MD, K4/918 University of Wisconsin Hospital, 600 Highland Avenue, Madison, WI 53792–9988, USA Tel.: (608) 263-6201 Fax: (608) 265-2207 E-mail: gern@medicine.wisc.edu Accepted 3 March 2002 Pediatr Allergy Immunol 2002: 13: 386–393 Printed in UK. All rights reserved Copyright Ó 2002 Blackwell Munksgaard PEDIATRIC ALLERGY AND IMMUNOLOGY ISSN 0905-6157 386