Innate Immune Dysfunction is Associated with Enhanced Disease Severity In Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Mella, Cesar; Suarez-Arrabal, M. Carmen; Lopez, Santiago M C; Stephens, Julie; Fernández, Soledad; Hall, Mark W.; Ramilo, Octavio; Mejías, Asunción

doi:10.1093/infdis/jis721

Cited by 100 publications

(105 citation statements)

References 35 publications

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“…In each of the patients, serum S-ASM was measured on two occasions throughout the clinical course, shown by days from admission. (Mella et al 2013). S-ASM is also known to be a cytokineresponsive enzyme that increases upon stimulation with interleukin (IL)-1β or tumor necrosis factor-α (TNF-α) (Marathe et al 1998).…”

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confidence: 99%

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

Yoshida

Noguchi

Kikuchi³

et al. 2017

Tohoku J. Exp. Med.

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Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p < 0.05). In the other illness groups, the serum S-ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

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confidence: 99%

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

Yoshida

Noguchi

Kikuchi³

et al. 2017

Tohoku J. Exp. Med.

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“…Evidence from both functional and genetic associations studies suggest that disease severity in viral bronchiolitis is influenced by the host's innate immune response [6,7]. Natural killer (NK) cells are innate lymphocytes and are "first responders" against infection [8].…”

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confidence: 99%

Interleukin-15 is associated with disease severity in viral bronchiolitis

et al. 2015

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Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity.A prospective single-centre observational study was conducted in a university-affiliated paediatric teaching hospital, comparing children (0-18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants.Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de-regulated miRNA were differentially expressed in bronchiolitis, including JAK3, STAT5A and NFKB1 on the IL-15 signalling pathway.IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis.@ERSpublications Interleukin-15 influences the host innate response and is associated with disease severity in viral bronchiolitis

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“…Critical illness-induced immune suppression has been demonstrated in children and adults with a variety of diagnoses, including trauma, 4,5 sepsis, [6][7][8] pancreatitis, 9,10 severe viral infections, 11,12 and following cardiopulmonary bypass. 13,14 The clinical consequences of immune suppression in the ICU setting include increased risk of multiple organ dysfunction syndrome, 15 increased susceptibility to secondary bacterial infections, 4,7,16 reactivation of latent viruses, 17 susceptibility to opportunistic organisms, 18,19 and increased risk of death.…”

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confidence: 99%

Critical Illness–Induced Immune Suppression: Current State of the Science

Greathouse

Hall

2016

American Journal of Critical Care

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Critical illness comprises a heterogeneous group of serious medical conditions that typically involve an initial proinflammatory process. A compensatory anti-inflammatory response may occur that, if severe and persistent, places the patient at high risk for adverse outcomes including secondary infection and death. Monitoring strategies can identify these patients through measurement of innate and adaptive immune function. Reductions in monocyte HLA-DR expression, reduced cytokine production capacity, increased inhibitory cell surface molecule expression, and lymphopenia have all been associated with this immunesuppressed state. Intriguing data suggest that critical illness-induced immune suppression may be reversible with agents such as interferon-γ, granulocyte macrophage colony-stimulating factor, interleukin 7, or anti-programmed death-1 therapy. Future approaches for characterization of patient-specific immune derangements and individualized treatment could revolutionize how we recognize and prevent complications in critically ill patients.

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Innate Immune Dysfunction is Associated with Enhanced Disease Severity In Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Cited by 100 publications

References 35 publications

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis

Interleukin-15 is associated with disease severity in viral bronchiolitis

Critical Illness–Induced Immune Suppression: Current State of the Science

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