Intensive Cytokine induction in Pandemic H1N1 Influenza Virus Infection Accompanied by Robust Production of IL-10 and IL-6

Yu, Xuelian; Zhang, Xi; Zhao, Bin; Wang, Jiayu; Zhu, Zhou; Teng, Zheng; Shao, Junjie; Shen, Jiaren; Gao, Ye; Yuan, Zhigang; Wu, Fan

doi:10.1371/journal.pone.0028680

Cited by 114 publications

(140 citation statements)

References 21 publications

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“…A significant elevation of IL-6, IL-10, and TNF-α levels was observed in H1N1 infected patients. The enhanced cytokine expression during H1N1 virus infection is in concordance with other human studies (Arankalle et al, 2010;Hasegawa et al, 2011;Yu et al, 2011). It has also been reported that IL-6 might act as the mediator in induction of IL-10 production, which leads to disease progression (Yu et al, 2011).…”

Section: Discussionsupporting

confidence: 88%

“…In general, the innate immune system is the first line of defense against viruses by induction of the expression of cytokines and chemokines (Yu et al, 2011). Cytokine activation usually occurs much earlier than the clinically observable response, and it may play an important role in stimulating an immune response to the H1N1 virus infection (Wen et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, influenza virus enhances the induction of proinflammatory cytokines, including IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α, which may lead to disease progression (Arankalle et al, 2010;Damjanovic et al, 2011;Gao et al, 2011;Hasegawa et al, 2011;Yu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus

Lim¹,

Oh²,

Kim³

et al. 2014

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Summary. -Influenza virus is well known for pandemics and epidemics with high morbidity. Many studies have been focused to this problematics, however, oxidative damage to DNA, lipids, and proteins and the expression of cytokines, antioxidant enzymes and heat-shock proteins (HSPs) in H1N1 virus-infected patients has not been investigated yet. Therefore we aimed this study at these issues. We found out that patients infected with the 2011 H1N1 virus as compared to control subjects exhibited an increased oxidative damage to DNA, lipids and proteins as assayed by levels of 8-hydroxydeoxyguanosine (8-OhdG) and malondialdehyde (MDA) and carbonyl content in plasma and urine. Moreover, the levels of antioxidant enzymes SOD and catalase, cytokines Il-6, 1L-10 and TNF-α and HSPs 90 and 27 were also significantly higher in the H1N1-infected patients. Our results suggest that the influenza H1N1 virus is a strong inducer of (i) oxidative damage to DNA, lipids, and proteins, (ii) antioxidant enzymes, (iii) cytokines and (iv) HSPs.Keywords: influenza H1N1 virus; patients; oxidative damage; antioxidant enzymes; cytokines; heat-shock proteins * Corresponding authors. E-mail: dsul@korea.ac.kr, litjacob@chol. com; phone: +82-2-920-6614. # These authors contributed equally to this work. Abbreviations: 8-OhdG = 8-hydroxydeoxyguanosine; SOD = superoxide dismutase; IL = interleukin; TNF-α = tumor necrosis factor alpha; MDA = malondialdehyde; Prx = peroxiredoxin; HSPs = heat shock proteins; ROS = reactive oxygen species

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus

Lim¹,

Oh²,

Kim³

et al. 2014

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“…In addition, the levels of an anti-inflammatory cytokine, IL-10, were high in an unimmunized WT group compared to immunized WT and CD47KO groups, suggesting that IL-10 may be required to downregulate excessive lung inflammation in a naive host after infection. In support of our observation, a study suggested that a high IL-10 level may be an indicator of disease progression and severity (46). Defective neutrophil migration was observed in the absence of CD47 expression (13).…”

Section: Discussionsupporting

confidence: 85%

CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus

Lee

et al. 2016

J Virol

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An integrin-associated protein CD47, which is a ligand for the inhibitory receptor signal regulatory protein ␣, is expressed on B and T cells, as well as on most innate immune cells. However, the roles of CD47 in the immune responses to viral infection or vaccination remain unknown. We investigated the role of CD47 in inducing humoral immune responses after intranasal infection with virus or immunization with influenza virus-like particles (VLPs). Virus infection or vaccination with VLPs containing hemagglutinin from A/PR8/34 influenza virus induced higher levels of antigen-specific IgG2c isotype dominant antibodies in CD47-deficient (CD47KO) mice than in wild-type (WT) mice. CD47KO mice with vaccination showed greater protective efficacy against lethal challenge, as evidenced by no loss in body weight and reduced lung viral titers compared to WT mice. In addition, inflammatory responses which include cytokine production, leukocyte infiltrates, and gamma interferon-producing CD4 ؉ T cells, as well as an anti-inflammatory cytokine (interleukin-10), were reduced in the lungs of vaccinated CD47KO mice after challenge with influenza virus. Analysis of lymphocytes indicated that GL7 ؉ germinal center B cells were induced at higher levels in the draining lymph nodes of CD47KO mice compared to those in WT mice. Notably, CD47KO mice exhibited significant increases in the numbers of antigen-specific memory B cells in spleens and plasma cells in bone marrow despite their lower levels of background IgG antibodies. These results suggest that CD47 plays a role as a negative regulator in inducing protective immune responses to influenza vaccination. I nfluenza viruses are common pathogens in the respiratory tract that are highly contagious and can cause pulmonary diseases. Seasonal influenza virus variants annually cause significant levels of morbidity and mortality, mostly in infants, the elderly, and sick people (1, 2). Vaccination is the most effective measure to prevent infections with a variety of pathogens, including influenza virus. Virus-like particles (VLPs) are able to effectively stimulate antigen-presenting cells (APCs), which in turn activate T and B cells (3-6). It has been demonstrated that immunization with influenza VLPs can induce protective humoral responses against seasonal and pandemic influenza virus infections (7-9). However, the mechanisms for evoking long-lasting immune responses are largely unknown.CD47 is a transmembrane protein, which is first identified as integrin ␣v␤3. CD47 that is expressed on hematopoietic and nonhematopoietic cells can interact with an inhibitory receptor signal regulatory protein ␣ (SIRP␣) (10). SIRP␣ is also expressed on dendritic cells (DCs) and macrophages, whereas SIRP␣ is barely expressed on B and T cells (11,12). It has been demonstrated that CD47/CD47 and CD47/SIRP␣ interactions are important for DC and neutrophil migration (13,14). In addition, CD11b ϩ DCs in the lungs express both CD47 and SIRP␣, but CD103 ϩ DCs express only CD47. It was also demonstrated t...

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“…21,22 ). There are significant changes in cytokines and chemokines in patients with H1N1 influenza even with mild symptoms 23 . The influenza H1N1 pandemic occurred in 2009, and was associated elsewhere with significantly higher ma- ternal morbidity and mortality 24 .…”

Section: Discussionmentioning

confidence: 99%

Amniotic fluid embolism - Investigation of fatal cases in Slovakia in the years 2005-2010 compared with fatal cases in the United Kingdom

Krištúfková¹,

Borovský²,

Korbeľ³

et al. 2014

BIOMED PAP

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Background. Amniotic fluid embolism (AFE) is a rare, often severe complication of pregnancy. The clinical diagnosis is difficult to establish and is one of exclusion. The aim of this study was to investigate 6 fatal cases of AFE in Slovakia and compare the incidence, risk factors, course, management and neonatal outcomes with fatal cases of AFE in the United Kingdom (UK). Materials and Methods. Data on fatal cases of AFE in Slovakia were analysed and compared with fatal cases in the UK in the years 2005-2010. Results. The incidence in Slovakia was significantly higher than in the UK from 2005-2010 (RR 5.03, 95% CI 1.98-12.75, P=0.003). However, 5/6 deaths occurred in 2009 coinciding with the H1N1 flu virus pandemic in Slovakia. There were no significant differences in the characteristics of women who died, with the exception of gestational age at delivery; significantly higher in Slovakia (median 41 versus 39 weeks, P=0.01). In Slovakia most of the cases occurred after delivery, 83.3%, compared with 52.9% in the UK. There were no significant differences in clinical signs, use of recombinant factor VIIa or performance of obstetric hysterectomy. In Slovakia 83.3% and in the UK 94.7% of infants survived, but 20% and 27.8% had some long-term sequelae. Conclusion. AFE is now the leading cause of maternal deaths in Slovakia. However, we found no significant differences in the possible risk factors, course, management or outcomes between Slovakia and the UK. This analysis is limited by study power; we propose that establishment of a national register of cases of AFE in Slovakia would help further investigate and monitor mortality from this condition.Key words: amniotic fluid embolism, incidence of amniotic fluid embolism, risk factors of amniotic fluid embolism, maternal mortality, neonatal outcome by amniotic fluid embolism

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Intensive Cytokine induction in Pandemic H1N1 Influenza Virus Infection Accompanied by Robust Production of IL-10 and IL-6

Cited by 114 publications

References 21 publications

Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus

Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus

CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus

Amniotic fluid embolism - Investigation of fatal cases in Slovakia in the years 2005-2010 compared with fatal cases in the United Kingdom

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