Differences in serum cytokine levels between influenza virus A and B infections in children.
ABSTRACT To investigate differences in cytokine production between influenza A and B.
thirty one patients with influenza A and 16 with influenza B were enrolled in this study. We measured soluble tumor necrosis factor receptor (sTNFR) 1, interleukin (IL)-6, interferon (IFN)-gamma and IL-4 concentrations in serum obtained from all patients during the acute and convalescence phases of their illnesses.
the sTNFR1 and IL-6 serum concentrations of patients with influenza A and B were equivalently elevated in the acute phase of their illness. However, the acute phase concentrations of IFN-gamma and IL-4 were significantly higher in patients with influenza A than in patients with influenza B. The concentration of all cytokines in influenza A and sTNFR1 in influenza B significantly decreased from the acute to convalescent phase. Plotted from the onset of symptoms it appeared that all of the cytokines peaked within 24h after onset.
the production pattern of the inflammatory cytokines - TNF and IL-6 - were the same between influenza A and B. However, a Th2 predominant cytokine pattern was induced after natural influenza virus A infection, notably IL-4 that differed from that to influenza B.
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ABSTRACT: The objective of this study was to estimate the efficacy of the neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir for decreasing viral load and to investigate whether NAI treatment decreases viral susceptibility to NAIs over time in children with influenza B virus infection. Of 27 patients with influenza B virus infection, 8 and 9 were treated with oseltamivir and zanamivir, respectively, whereas 10 received no NAI. Nasal aspiration samples, collected every morning until negative antigen results in two consecutive samples were observed, were subjected to viral load measurements by quantitative real-time reverse transcription-polymerase chain reaction and viral susceptibility to NAI by NA inhibition assays. Viral load decreased in both the oseltamivir and zanamivir groups by day 2 but increased in the no-NAI treatment group. Viral load in the oseltamivir and zanamivir groups on day 5 was 2.6% and 9.2% of that on day 0, respectively, whereas it was 26.4% in the no-NAI treatment group. Mean 50% inhibitory concentration (IC50) values of oseltamivir and zanamivir in the no-NAI treatment group were 5.0-6.6 and 1.3-1.8 nM, respectively. Mean IC50 values of oseltamivir and zanamivir in patients treated with oseltamivir and zanamivir were 3.9-8.8 and 1.3-1.8 nM, respectively. No major decrease in viral susceptibility to NAIs was observed during or after NAI treatment. NAI treatment was effective for inhibiting viral replication during the early days of illness and did not decrease viral susceptibility to NAIs in patients with influenza B virus infection.The Pediatric Infectious Disease Journal 01/2014; 33(7). DOI:10.1097/INF.0000000000000266 · 3.14 Impact Factor
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ABSTRACT: Rationale: Children are an at-risk population for developing complications following influenza infection, but immunological correlates of disease severity are not understood. We hypothesized that innate cellular immune responses at the site of infection would correlate with disease outcome. Objectives: To test the immunological basis of severe illness during natural influenza virus infection of children and adults at the site of infection. Methods: An observational cohort study with longitudinal sampling of peripheral and mucosal sites in 84 naturally influenza-infected individuals, including infants. Cellular responses, viral loads, and cytokines were quantified from nasal lavages and blood, and correlated to clinical severity. Measurements and Main Results: We show for the first time that while viral loads in children and adults were similar, innate responses in the airways were stronger in children and varied considerably between plasma and site of infection. Adjusting for age and viral load, an innate immune profile characterized by increased nasal lavage MCP-3, IFNα2 and plasma IL-10 levels at enrollment predicted progression to severe disease. Increased plasma IL-10, MCP-3, and IL-6 levels predicted hospitalization. This inflammatory cytokine production correlated significantly with monocyte localization from the blood to the site of infection, with conventional monocytes positively correlating with inflammation. Increased frequencies of CD14lo monocytes were in the airways of participants with lower inflammatory cytokine levels. Conclusions: An innate profile was identified that correlated with disease progression independent of viral dynamics and age. The airways and blood displayed dramatically different immune profiles emphasizing the importance of cellular migration and localized immune phenotypes.American Journal of Respiratory and Critical Care Medicine 12/2013; 189(4). DOI:10.1164/rccm.201309-1616OC · 11.04 Impact Factor
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ABSTRACT: To evaluate the correlation between cytokine and neurotrophin expression and clinical findings, disease severity, and outcome of children with H1N1 influenza infection. A prospective observational clinical study was performed on 15 children with H1N1 infection, 15 controls with lower respiratory tract infections (LRTI), and 15 non-infected children. Plasma levels of interleukin (IL)-1β, IL-6, and neurotrophic factor (nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial derived neurotrophic factor (GDNF)) were measured using immunoenzymatic assays. Significantly higher levels of IL-1β, IL-6, BDNF, and NGF were detected in patients with H1N1 infection compared to LRTI controls, while there was no significant variation in GDNF in the two groups. IL-1β, IL-6, BDNF, and NGF levels were significantly higher in H1N1 patients with more severe clinical manifestations compared to H1N1 patients with mild clinical manifestations. Of note, IL-6 was significantly correlated with the severity of respiratory compromise and fever, while NGF up-regulation was associated with the duration of cough. No correlation was found between interleukin and neurotrophic factor expression and outcome. H1N1 infection induces an early and significant IL-1β, IL-6, BDNF, and NGF up-regulation. The over-expression of these molecular markers is likely to play a neuroimmunomodulatory role in H1N1 infection and may contribute to airway inflammation and bronchial hyper-reactivity in infected children.International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 09/2013; 17(12). DOI:10.1016/j.ijid.2013.07.006 · 2.17 Impact Factor