title: Inflammatory profiles in severe pneumonia associated with the pandemic influenza A/H1N1 virus isolated in Mexico City.
abstract: The immune mechanisms underlying the pathogenesis of severe pneumonia associated with the A/H1N1 virus are not well known. The objective of this study was to determine whether severe A/H1N1-associated pneumonia can be explained by the emergence of particular T-cell subsets and the cytokines/chemokines they produced, as well as distinct responses to infection. T-cell subset distribution and cytokine/chemokine levels in peripheral blood and bronchoalveolar lavage (BAL) were determined in patients with severe A/H1N1 infection, asymptomatic household contacts, and healthy controls. Cytokine and chemokine production was also evaluated after in vitro infection with seasonal H1N1 and pandemic A/H1N1 strains. We found an increase in the frequency of peripheral Th2 and Tc2 cells in A/H1N1 patients. A trend toward increased Tc1 cells was observed in household contacts. Elevated serum levels of IL-6, CXCL8, and CCL2 were found in patients and a similar cytokine/chemokine profile was observed in BAL, in which CCL5 was also increased. Infection assays revealed that both strains induce the production of several cytokines/chemokines at 24 and 72 h, however, IL-6, CCL3, and CXCL8 were strongly up-regulated in 72-h cultures in presence of the A/H1N1 virus. Several inflammatory mediators are up-regulated in peripheral and lung samples from A/H1N1-infected patients who developed severe pneumonia. In addition, the A/H1N1 strain induces higher levels of pro-inflammatory cytokines and chemokines than the seasonal H1N1 strain. These findings suggest that it is possible to identify biomarkers of severe pneumonia and also suggest the therapeutic use of immunomodulatory drugs in patients with severe pneumonia associated with A/H1N1 infection.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico DF, Mexico. joazu@yahoo.com
authors.forename: Joaquín
authors.initials: J
authors.lastname: Zúñiga
authors.forename: Martha
authors.initials: M
authors.lastname: Torres
authors.forename: Javier
authors.initials: J
authors.lastname: Romo
authors.forename: Diana
authors.initials: D
authors.lastname: Torres
authors.forename: Luis
authors.initials: L
authors.lastname: Jiménez
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ramírez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cruz
authors.forename: Enrique
authors.initials: E
authors.lastname: Espinosa
authors.forename: Teresa
authors.initials: T
authors.lastname: Herrera
authors.forename: Ivette
authors.initials: I
authors.lastname: Buendía
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramírez-Venegas
authors.forename: Yolanda
authors.initials: Y
authors.lastname: González
authors.forename: Karen
authors.initials: K
authors.lastname: Bobadilla
authors.forename: Fernando
authors.initials: F
authors.lastname: Hernández
authors.forename: Jorge
authors.initials: J
authors.lastname: García
authors.forename: Francisco
authors.initials: F
authors.lastname: Quiñones-Falconi
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sada
authors.forename: María E
authors.initials: ME
authors.lastname: Manjarrez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cabello
authors.forename: Simón
authors.initials: S
authors.lastname: Kawa
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Annie
authors.initials: A
authors.lastname: Pardo
authors.forename: Moisés
authors.initials: M
authors.lastname: Selman
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004196:Disease Outbreaks; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D007251:Influenza, Human / Q000150:complications* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D008297:Male; D008800:Mexico; D011024:Pneumonia, Viral / Q000276:immunology / Q000821:virology*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D012367:RNA, Viral