Cytokine gene polymorphisms moderate responses to respiratory syncytial virus in adults

被引:32
作者
Gentile, DA
Doyle, WJ
Zeevi, A
Piltcher, O
Skoner, DP
机构
[1] Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15213 USA
[2] Childrens Hosp Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15260 USA
关键词
respiratory syncytial virus; illness; cytokines; genotypes;
D O I
10.1016/S0198-8859(02)00705-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immune responses and illness severity during viral upper respiratory infections may be influenced by the local elaboration of cytokines. Cytokine gene polymorphisms moderate immune responses and severity of illness in various inflammatory and infectious diseases. We performed cytokine genotyping on 29 adults experimentally inoculated with respiratory syncytial virus (RSV) to determine whether specific cytokine gene polymorphisms are associated with immune responses or illness severity. DNA was extracted from leukocytes and assayed for TNF-alpha, IFN-gamma, IL-6, IL-10 and TGF-beta1 genotypes using polymerase chain reaction-sequence-specific primer technology. Outcomes consisted of baseline and convalescent RSV-specific serum IgG and nasal IgA titers, nasal secretion weights, nasal, throat and general symptom scores, and nasal cytokine protein levels. IFN-gamma genotype was directly related with the frequency of subjects having at least a four-fold increase in RSV-specific serum IgG and TNF-alpha genotype was inversely associated with the frequency of subjects having at least a twofold increase in RSV-specific nasal IgA. Additionally, IL-6 genotype was predictive of certain measures of illness expression, while IFN-gamma genotype predicted IL-1 protein levels, and TNF-alpha genotype predicted IL-6 and IL-8 protein levels in nasal lavage fluids. There were no associations between IL-10 or TGF-beta1 and any of the outcome parameters. These results suggest that certain cytokine gene polymorphisms moderate immune responses and illness severity in adults experimentally exposed to RSV. (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Science Inc.
引用
收藏
页码:93 / 98
页数:6
相关论文
共 20 条
[1]   MICRONEUTRALIZATION TEST FOR RESPIRATORY SYNCYTIAL VIRUS BASED ON AN ENZYME-IMMUNOASSAY [J].
ANDERSON, LJ ;
HIERHOLZER, JC ;
BINGHAM, PG ;
STONE, YO .
JOURNAL OF CLINICAL MICROBIOLOGY, 1985, 22 (06) :1050-1052
[2]  
AWAD RA, 2001, J HEART LUNG TRANSPL, V20, P265
[3]   Nasal and otologic effects of experimental respiratory syncytial virus infection in adults [J].
Buchman, CA ;
Doyle, WJ ;
Pilcher, O ;
Gentile, DA ;
Skoner, DP .
AMERICAN JOURNAL OF OTOLARYNGOLOGY, 2002, 23 (02) :70-75
[4]  
Carlsen K H, 1994, Pediatr Allergy Immunol, V5, P48, DOI 10.1111/j.1399-3038.1994.tb00348.x
[5]  
Eigen H, 1999, J PEDIATR-US, V135, pS1
[6]   The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis [J].
Fishman, D ;
Faulds, G ;
Jeffery, R ;
Mohamed-Ali, V ;
Yudkin, JS ;
Humphries, S ;
Woo, P .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (07) :1369-1376
[7]   Increased interleukin-6 levels in nasal lavage samples following experimental influenza A virus infection [J].
Gentile, D ;
Doyle, W ;
Whiteside, T ;
Fireman, P ;
Hayden, FG ;
Skoner, D .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 1998, 5 (05) :604-608
[8]   Prevalence of various respiratory viruses in the middle ear during acute otitis media [J].
Heikkinen, T ;
Thint, M ;
Chonmaitree, T .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (04) :260-264
[9]   Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions [J].
Hornsleth, A ;
Klug, B ;
Nir, M ;
Johansen, J ;
Hansen, KS ;
Christensen, LS ;
Larsen, LB .
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 1998, 17 (12) :1114-1121
[10]   Symptom pathogenesis during acute influenza: Interleukin-6 and other cytokine responses [J].
Kaiser, L ;
Fritz, RS ;
Straus, SE ;
Gubareva, L ;
Hayden, FG .
JOURNAL OF MEDICAL VIROLOGY, 2001, 64 (03) :262-268