Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1518-1523

Monocyte IL-10 Production during Respiratory Syncytial Virus Bronchiolitis Is Associated with Recurrent Wheezing in a One-Year Follow-up Study

LOUIS BONT, COBI J. HEIJNEN, ANNEMIEKE KAVELAARS, WIM M. C. van AALDEREN, FRANK BRUS, JOS Th. M. DRAAISMA, SIBYL M. GEELEN, and JAN L. L. KIMPEN

University Hospital for Children and Youth "Het Wilhelmina Kinderziekenhuis," Utrecht; Academic Medical Center, Amsterdam; Department of Pediatrics, Rijnstate Hospital, Arnhem; and Department of Pediatrics, St. Elisabeth Hospital, Tilburg, The Netherlands

Respiratory syncytial virus (RSV) bronchiolitis is associated with subsequent recurrent wheezing episodes. To determine whether cytokine responses during infection can be of predictive value for the development of recurrent wheezing, we performed a follow-up study in 50 hospitalized children with RSV bronchiolitis. Monocyte and lymphocyte cytokine responses in vitro were studied during the acute phase of disease, and again during the convalescent phase, 3 to 4 wk later. Monocyte cytokine responses, including interleukin-10 (IL-10), were measured in whole blood cultures, stimulated with lipopolysaccharide and interferon- (LPS + IFN-). In addition, T-cell cytokine responses, including IFN- and IL-4 production, were measured in whole-blood cultures stimulated with phytohemagglutinin (PHA) or CD2 + CD28. Cytokine responses were analyzed in relation to the development of recurrent episodes of wheezing, documented by parents in a diary during a 1-yr follow-up period. IL-10 responses during the acute phase of RSV bronchiolitis were comparable to those in healthy control subjects. During the convalescent phase, IL-10 responses were significantly increased in patients as compared with those in healthy control subjects (p < 0.001). At follow-up, 27 children (58%) had recurrent episodes of wheezing. IL-10 levels, measured during the convalescent phase, were significantly higher in patients who developed recurrent wheezing during the year after RSV bronchiolitis than in patients without recurrent episodes of wheezing (p = 0.006). Moreover, IL-10 responses during the convalescent phase correlated significantly with the number of wheezing episodes (r = 0.42, n = 46, p = 0.004). Interestingly, no association was found between IFN- responses, IL-4 responses, or IFN/IL-4 ratios and recurrent wheezing. We conclude that monocyte IL-10 responses in vitro upon stimulation with nonspecific stimuli may have predictive value for the development of recurrent wheezing after RSV bronchiolitis. Moreover, our results indicate that not only allergen-driven Th2 cytokine responses can lead to asthmatic symptoms but also virus-induced changes in cytokine responses may result in asthmatic symptoms.

This article has been cited by other articles:

				M. J J Ermers, M. M Rovers, J. B van Woensel, J. L L Kimpen, L. J Bont, and on behalf of the RSV Corticosteroid Study Group The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial BMJ, March 31, 2009; 338(mar31_2): b897 - b897. [Abstract] [Full Text] [PDF]

				L. C. Denlinger, L. Shi, A. Guadarrama, K. Schell, D. Green, A. Morrin, K. Hogan, R. L. Sorkness, W. W. Busse, and J. E. Gern Attenuated P2X7 Pore Function as a Risk Factor for Virus-induced Loss of Asthma Control Am. J. Respir. Crit. Care Med., February 15, 2009; 179(4): 265 - 270. [Abstract] [Full Text] [PDF]

				J Mallol, J A Castro-Rodriguez, E Cortez, V Aguirre, P Aguilar, and L Barrueto Heightened bronchial hyperresponsiveness in the absence of heightened atopy in children with current wheezing and low income status Thorax, February 1, 2008; 63(2): 167 - 171. [Abstract] [Full Text] [PDF]

				A. M. Singh, P. E. Moore, J. E. Gern, R. F. Lemanske Jr., and T. V. Hartert Bronchiolitis to Asthma: A Review and Call for Studies of Gene-Virus Interactions in Asthma Causation Am. J. Respir. Crit. Care Med., January 15, 2007; 175(2): 108 - 119. [Abstract] [Full Text] [PDF]

				N. W. Lukacs, M. L. Moore, B. D. Rudd, A. A. Berlin, R. D. Collins, S. J. Olson, S. B. Ho, and R. S. Peebles Jr Differential Immune Responses and Pulmonary Pathophysiology Are Induced by Two Different Strains of Respiratory Syncytial Virus Am. J. Pathol., September 1, 2006; 169(3): 977 - 986. [Abstract] [Full Text] [PDF]

				F. D. Martinez Heterogeneity of the Association between Lower Respiratory Illness in Infancy and Subsequent Asthma Proceedings of the ATS, August 1, 2005; 2(2): 157 - 161. [Abstract] [Full Text] [PDF]

				J. Y. Richardson, M. G. Ottolini, L. Pletneva, M. Boukhvalova, S. Zhang, S. N. Vogel, G. A. Prince, and J. C. G. Blanco Respiratory Syncytial Virus (RSV) Infection Induces Cyclooxygenase 2: A Potential Target for RSV Therapy J. Immunol., April 1, 2005; 174(7): 4356 - 4364. [Abstract] [Full Text] [PDF]

				L Bont, M Steijn, W M C van Aalderen, F Brus, J M Th Draaisma, R A A M Van Diemen-Steenvoorde, M Pekelharing-Berghuis, and J L L Kimpen Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection Thorax, June 1, 2004; 59(6): 512 - 516. [Abstract] [Full Text] [PDF]

				R. F. Lemanske Jr. Does Respiratory Syncytial Viral-induced Bronchiolitis Result from Helper T Cell Type 1/Type 2 Cytokine Imbalance? Am. J. Respir. Crit. Care Med., September 15, 2003; 168(6): 625 - 627. [Full Text] [PDF]

				R. J. Singleton, G. J. Redding, T. C. Lewis, P. Martinez, L. Bulkow, B. Morray, H. Peters, J. Gove, C. Jones, D. Stamey, et al. Sequelae of Severe Respiratory Syncytial Virus Infection in Infancy and Early Childhood Among Alaska Native Children Pediatrics, August 1, 2003; 112(2): 285 - 290. [Abstract] [Full Text] [PDF]

				C. G. Lee, R. J. Homer, L. Cohn, H. Link, S. Jung, J. E. Craft, B. S. Graham, T. R. Johnson, and J. A. Elias Transgenic Overexpression of Interleukin (IL)-10 in the Lung Causes Mucus Metaplasia, Tissue Inflammation, and Airway Remodeling via IL-13-dependent and -independent Pathways J. Biol. Chem., September 13, 2002; 277(38): 35466 - 35474. [Abstract] [Full Text] [PDF]

				G. Piedimonte and E.A.F. Simoes Respiratory syncytial virus and subsequent asthma: one step closer to unravelling the Gordian knot? Eur. Respir. J., September 1, 2002; 20(3): 515 - 517. [Full Text] [PDF]

				K-;H. Carlsen and P.J. Sterk Infection: friend or foe to the development of asthma? Eur. Respir. J., November 1, 2001; 18(5): 744 - 747. [Full Text] [PDF]

				M. J. TOBIN Pediatrics, Surfactant, and Cystic Fibrosis in AJRCCM 2000 Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1581 - 1594. [Full Text] [PDF]

				R. L. RILEY What Nobody Needs to Know About Airborne Infection Am. J. Respir. Crit. Care Med., January 1, 2001; 163(1): 7 - 8. [Full Text]

				R. P. Garofalo and H. Haeberle Epithelial Regulation of Innate Immunity to Respiratory Syncytial Virus Am. J. Respir. Cell Mol. Biol., November 1, 2000; 23(5): 581 - 585. [Full Text]