Abstract

Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 - 36 months and to relate their responses to disease severity. Methods: Nasopharyngeal aspirations (NPAs) were analyzed for RSV and IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-1RA, IL-4R, IFN-, sTNFR1, sTNFR2, and TNF-α. Clinical data were collected from the medical records. Results: We included 331 infants of whom 214 were RSV+. In comparison to RSV- infants, they had significantly higher levels of TNF-, IL-6, IL-1, and IFN- (p < 0.05). This also applied to anti-inflammatory cytokine IL-10 levels, but these levels were remarkably lower than levels of TNF-, IL-6, and IL-1. sTNFR1/2 were significantly increased in RSV+ infants. Hospitalized patients had significantly higher levels of TNF-, sTNFR2, and IL-10 (p < 0.05) than non-hospitalized patients. The cytokine response could not be related to disease severity. We found no evidence of a skewed Th1/Th2 immune profile. Conclusion: In acute RSV disease, infected infants’ NPAs contain a significant amount of pro-inflammatory cytokines. Whether this response is beneficial or deleterious remains unanswered. Interpersonal variations in cytokine responses might be linked to an inherited tendency to variations in disease severity.

Highlights

  • Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response

  • A number of findings suggest that the variability in the severity of respiratory syncytial virus (RSV) infections may be rooted in individual differences in inflammatory response [1,2] and not to RSV polymorphisms

  • In vivo human studies of cytokine levels in airway specimens from RSV+ infants indicate a pronounced production of inflammatory and immunoregulating cytokines such as interleukin (IL-)-2, IL-5, IL-6, IL-8, IL-9, IL-10, IL-11, tumor necrosis factor (TNF), Regulated on Activation Normal T-cell Expressed and Secreted (RANTES), and Eosinophil Cationic Protein (ECP) [11,12,13]

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Summary

Introduction

Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. A number of findings suggest that the variability in the severity of respiratory syncytial virus (RSV) infections may be rooted in individual differences in inflammatory response [1,2] and not to RSV polymorphisms (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genome& Cmd=ShowDetailView&TermToSearch=11728). In vivo human studies of cytokine levels in airway specimens from RSV+ infants indicate a pronounced production of inflammatory and immunoregulating cytokines such as interleukin (IL-)-2, IL-5, IL-6, IL-8, IL-9, IL-10, IL-11, tumor necrosis factor (TNF), Regulated on Activation Normal T-cell Expressed and Secreted (RANTES), and Eosinophil Cationic Protein (ECP) [11,12,13]. The clinical significance has been difficult to ascertain since the majority of these studies report unsystematic measurements of cytokine candidates in small groups of patients. Only a few studies have included an appropriate control group

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