Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 6/2010

Open Access 01-12-2010 | Research

Clinical aspects and cytokine response in severe H1N1 influenza A virus infection

Authors: Natalia Hagau, Adriana Slavcovici, Daniel N Gonganau, Simona Oltean, Dan S Dirzu, Erika S Brezoszki, Mihaela Maxim, Constantin Ciuce, Monica Mlesnite, Rodica L Gavrus, Carmen Laslo, Radu Hagau, Magda Petrescu, Daniela M Studnicska

Published in: Critical Care | Issue 6/2010

Login to get access

Abstract

Introduction

The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects.

Methods

Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively.

Results

In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO2:FiO2 ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS.

Conclusions

In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive correlation with the admission delay and C-reactive protein, and a negative correlation with the PaO2:FiO2 ratio. Obese patients with nvA(H1N1) disease have a significant level of IL-8. There are significant differences in the level of cytokines when comparing viral ARDS with bacterial ARDS.
Appendix
Available only for authorised users
Literature
1.
Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 influenza: Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 2010, 362: 1708-1719. 10.1056/NEJMra1000449CrossRef
2.
Louie JK, Acosta M, Winter K, Jean C, Gavali S, Schechter R, Vugia D, Harriman K, Matyas B, Glaser CA, Samuel MC, Rosenberg J, Talarico J, Hatch D, California Pandemic (H1N1) Working Group: Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA 2009, 302: 1896-1902. 10.1001/jama.2009.1583CrossRefPubMed
3.
Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, Sugerman DE, Druckenmiller JK, Ritger KA, Chugh R, Jasuja S, Deutscher M, Chen S, Walker JD, Duchin JS, Lett S, Soliva S, Wells EV, Swerdlow D, Uyeki TM, Fiore AE, Olsen SJ, Fry AM, Bridges CB, Finelli L, 2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team: Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009, 361: 1935-1944. 10.1056/NEJMoa0906695CrossRefPubMed
4.
Dominguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinoza-Perez L, de la Torre A, Poblano-Morales M, Baltazar-Torres JA, Bautista E, Martinez A, Martinez MA, Rivero E, Valdez R, Ruiz-Palacios G, Hernandez M, Stewart TE, Fowler RA: Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA 2009, 302: 1880-1887. 10.1001/jama.2009.1536CrossRefPubMed
5.
The ANZIC Influenza Investigators: Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 2009, 361: 1925-1934. 10.1056/NEJMoa0908481CrossRef
6.
Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, Stelfox T, Bagshaw S, Choong K, Lamontagne F, Turgeon AF, Lapinsky S, Ahern SP, Smith O, Siddiqui F, Jouvet P, Khwaja K, McIntyre L, Menon K, Hutchinson J, Hornstein D, Joffe A, Lauzier F, Singh J, Karachi T, Wiebe K, Olafson K, Ramsey C, Sharma S, Dodek P, Canadian Critical Care Trials Group H1N1 Collaborative, et al.: Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 2009, 302: 1872-1879. 10.1001/jama.2009.1496CrossRefPubMed
7.
8.
To KK, Hung IF, Li IW, Lee KL, Koo CK, Yan WW, Liu R, Ho KY, Chu KH, Watt CL, Luk WK, Lai KY, Chow FL, Mok T, Buckley T, Chan JF, Wong SS, Zheng B, Chen H, Lau CC, Tse H, Cheng VC, Chan KH, Yuen KY, Pandemic H1N1 Study Group: Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis 2010, 50: 850-859. 10.1086/650581CrossRefPubMed
9.
Bermejo-Martin JF, de Lejarazu RO, Pumarola T, Rello J, Almansa R, Ramirez P, Martin-Loeches I, Varillas D, Gallegos MC, Seron C, Micheloud D, Gomez JM, Tenorio-Abreu A, Ramos MJ, Molina ML, Huidobro S, Sanchez E, Gordon M, Fernandez V, del Castillo A, Marcos MA, Villanueva B, Lopez CJ, Rodriguez-Dominguez M, Galan JC, Canton R, Lietor A, Rojo S, Eiros JM, Hinojosa C, et al.: Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Crit Care 2009, 13: R201. 10.1186/cc8208PubMedCentralCrossRefPubMed
10.
Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R: The American-European Consensus Conference on ARDS. Definition, mechanisms, relevant outcome, and clinical trial coordination. Am J Respir Crit Care Med 1994, 149: 818-824.CrossRefPubMed
11.
Offner PJ, Moore EE: Lung injury severity scoring in the era of lung protective mechanical ventilation: the PaO 2 /FiO 2 ratio. J Trauma 2003, 55: 285-289. 10.1097/01.TA.0000078695.35172.79CrossRefPubMed
12.
Gill JR, Sheng ZM, Ely SF, Guinee DG, Beasley MB, Suh J, Deshpande C, Mollura DJ, Morens DM, Bray M, Travis WD, Taubenberger JK: Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections. Arch Pathol Lab Med 2010, 134: 235-243.PubMedCentralPubMed
13.
Mauad T, Hajjar LA, Callegari GD, da Silva LF, Schout D, Galas FR, Alves VA, Malheiros DM, Auler JO Jr, Ferreira AF, Borsato MR, Bezerra SM, Gutierrez PS, Caldini ET, Pasqualucci CA, Dolhnikoff M, Saldiva PH: Lung pathology in fatal novel human influenza A(H1N1) infection. Am J Respir Crit Care Med 2010, 181: 72-79. 10.1164/rccm.200909-1420OCCrossRefPubMed
14.
Romagnani S: T-cell subsets (Th1 versus Th2). Ann Allergy Asthma Immunol 2000, 85: 9-18. 10.1016/S1081-1206(10)62426-XCrossRefPubMed
15.
Hamza T, Barnett JB, Li B: Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol Sci 2010, 11: 789-806. 10.3390/ijms11030789PubMedCentralCrossRefPubMed
16.
Palmer EM, Farrokh-Siar L, Maguire van Seventer J, van Seventer GA: IL-12 decreases activation-induced cell death in human naïve Th cells costimulated by intercellular adhesion molecule-1.I. IL-12 alters caspase processing and inhibits enzyme function. J Immunol 2001, 167: 749-758.CrossRefPubMed
17.
Pirtskhalaishvili G, Shurin GV, Esche C, Cai Q, Salup RR, Bykovskaia SN, Lotze MT, Shurin MR: Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins. Br J Cancer 2000, 83: 506-513. 10.1054/bjoc.2000.1289PubMedCentralCrossRefPubMed
18.
Grohmann U, Belladonna ML, Vacca C, Bianchi R, Fallarino F, Orabona C, Fioretti MC, Puccetti P: Positive regulatory role of IL-12 in macrophages and modulation by IFN-gamma. J Immunol 2001, 167: 221-227.CrossRefPubMed
19.
Brydon EW, Smith H, Sweet C: Influenza A virus-induced apoptosis in bronchiolar epithelial (NCI-H292) cells limits pro-inflammatory cytokine release. J Gen Virol 2003, 84: 2389-2400. 10.1099/vir.0.18913-0CrossRefPubMed
20.
Berard M, Brandt K, Bulfone Paus S, Tough D: IL-15 promotes the survival of naïve and memory phenotype CD8 + T cells. J Immunol 2003, 170: 5018-5026.CrossRefPubMed
21.
Yajima T, Yoshihara K, Nakazato K, Kumabe S, Koyasu S, Sad S, Shen H, Kuwano H, Yoshikai Y: IL-15 regulates CD8 + T cell contraction during primary infection. J Immunol 2006, 176: 507-515.CrossRefPubMed
22.
Nakamura R, Maeda N, Shibata K, Yamada H, Kase T, Yoshikai Y: Interleukin-15 is critical in the pathogenesis of influenza a virus-induced acute lung injury. J Virol 2010, 84: 5574-5582. 10.1128/JVI.02030-09PubMedCentralCrossRefPubMed
23.
Liu K, Catalfamo M, Li Y, Henkart PA, Weng NP: IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8 + memory T cells. Proc Natl Acad Sci USA 2002, 99: 6192-6197. 10.1073/pnas.092675799PubMedCentralCrossRefPubMed
24.
Miossec P, Korn T, Kuchroo VK: Interleukin-17 and Type 17 helper T cells. N Engl J Med 2009, 361: 888-898. 10.1056/NEJMra0707449CrossRefPubMed
25.
Korn T, Oukka M, Kuchroo V, Bettelli E: Th17 cells: effector T cells with inflammatory properties. Semin Immunol 2007, 19: 362-371. 10.1016/j.smim.2007.10.007PubMedCentralCrossRefPubMed
26.
McGill J, Heusel JW, Legge KL: Innate immune control and regulation of influenza virus infections. J Leukoc Biol 2009, 86: 803-812. 10.1189/jlb.0509368PubMedCentralCrossRefPubMed
27.
Straczkowski M, Straczkowska SD, Stepien A, Kowalska I, Szelachowska M, Kinalska I: Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-α system. J Clin Endocrinol Metab 2002, 87: 4602-4606. 10.1210/jc.2002-020135CrossRefPubMed
28.
Barnes PJ, Shapiro SD, Pauwels RA: Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 2003, 22: 672-688. 10.1183/09031936.03.00040703CrossRefPubMed
29.
Grumelli S, Corry DB, Song LZ, Song L, Green L, Huh J, Hacken J, Espada R, Bag R, Lewis DE, Kheradmand F: An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Med 2004, 1: e8. 10.1371/journal.pmed.0010008PubMedCentralCrossRefPubMed
30.
Dodd JS, Lum E, Goulding J, Muir R, Van Snick J, Openshaw PJM: IL -9 regulates pathology during primary and memory responses to respiratory syncytial virus infection. J Immunol 2009, 183: 7006-7013. 10.4049/jimmunol.0900085CrossRefPubMed
31.
Meduri GU, Tolley EA, Chrousos GP, Stentz F: Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome. Evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. Am J Respir Crit Care Med 2002, 165: 983-991.CrossRefPubMed
32.
Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R, Keh D, Kupfer Y, Oppert M, Meduri GU: Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA 2009, 301: 2362-2375. 10.1001/jama.2009.815CrossRefPubMed
Metadata
Title
Clinical aspects and cytokine response in severe H1N1 influenza A virus infection
Authors
Natalia Hagau
Adriana Slavcovici
Daniel N Gonganau
Simona Oltean
Dan S Dirzu
Erika S Brezoszki
Mihaela Maxim
Constantin Ciuce
Monica Mlesnite
Rodica L Gavrus
Carmen Laslo
Radu Hagau
Magda Petrescu
Daniela M Studnicska
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc9324

Other articles of this Issue 6/2010

Critical Care 6/2010 Go to the issue

Research

Renal replacement therapy is an independent risk factor for mortality in critically ill patients with acute kidney injury

Research

Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis

Research

Common NFKBIL2 polymorphisms and susceptibility to pneumococcal disease: a genetic association study

Research

Cross-comparison of cardiac output trending accuracy of LiDCO, PiCCO, FloTrac and pulmonary artery catheters

Research

Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated)

Research

Pre-hospital cooling of patients following cardiac arrest is effective using even low volumes of cold saline