Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children.
Profiling of immune mediators in both nasal and plasma samples is a common approach to the study of pathogenesis in respiratory viral infections. Nevertheless, mucosal immunity functions essentially independently from peripheral immunity. In our study, 27 immune mediators were profiled in parallel, in nasopharyngeal aspirates (NPAs) and plasma from 22 < 2 year-old children with a severe respiratory syncytial virus infection involving the lower respiratory tract, using a multiplex assay. NPAs from 22 children with innocent heart murmurs were used as controls. Differences in mediator concentrations between NPAs from patients and controls were assessed using the Mann-Whitney test. Ratios of innate/adaptive-immunity mediators, Th2/Th1-cytokines and CXC/CC-chemokines were calculated for NPAs and plasmas and differences were assessed using the Wilcoxon test. Associations mediators, severity and leukocyte counts were studied using the Spearman-Karber test.


RESULTS
increased levels of Th1 cytokines (IL-1beta, IL-2, IL-12p70, IFNgamma, TNFalpha), Th2 cytokines (IL-13, IL-4, IL-6, IL-10), chemokines (IP-10, IL-8, MIP1alpha, MIP-1beta), growth factors (FGFb, PDGFbb, GCSF) and IL-1RA, IL-17 were observed in patient NPAs in comparison to controls. In the relative comparisons between patient NPAs and plasmas, a predominance of innate immunity mediators, Th2 cytokines and CXC chemokines was found at the mucosal level. No association between the level of each mediator in NPAs and plasma was found. In plasma, PDGFbb, VEGF, MIP-1alpha, IL-8 correlated with severity; RANTES and IL-6 correlated with leukocyte counts.


CONCLUSIONS
acute respiratory syncytial virus infection induces a relative predominance of innate-immunity mediators, Th2 cytokines and CXC chemokines in the mucosal compartment in infected children.
Bermejo-Martin
Jesus F
JF
Lab. de Inmunología de Mucosas, Dept. of Pediatrics and Immunology. Universidad de Valladolid, Facultad de Medicina, Ramón y Cajal 7, Valladolid 47005, Spain. bermejo@ped.uva.es
Garcia-Arevalo
Maria C
MC
De Lejarazu
Raul Ortiz
RO
Ardura
Julio
J
Eiros
Jose M
JM
Alonso
Ana
A
Matías
Vanesa
V
Pino
Maria
M
Bernardo
David
D
Arranz
Eduardo
E
Blanco-Quiros
Alfredo
A
D000917:Antibody Formation / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D019743:Chemokines, CXC / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D009305:Nasopharynx / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000097:blood / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism