Role of TNF-alpha and its 55 and 75 kDa receptors in bronchial hyperreactivity.
The pathophysiological role of the tumour necrosis factor (TNF) system was studied in adults (n=37) and children (n=43) non asthmatic offspring of asthmatic parents with and without bronchial hyperreactivity proved by methacholine airway challenge test. SerumTNFalpha and its soluble receptors (sTNF-R1 and R2) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly elevated TNFalpha (adults: mean +/- SD=5.18 +/- 0.87 pg ml(-1), children: 5.08 +/- 1.78) vs. non-hyperreactives (adults: 4.12 +/- 0.43, P < 0.0001, children: 3.75 +/- 0.68, P=0.0084), sTNF-R1 (adults: 144 +/- 0.31 ng ml(-1), children: 1.30 +/- 0 25 vs. adults: 1.21 +/- 0.14, P=0.0305, children: 1.13+/-0.11 ng ml(-1), P=0.0042) and sTNF-R2 (adults: 0.85 +/- 0.40ng ml(-1), children: 0.70 +/- 0.46 vs. adults: 0.56 +/- 0.56 P=0.0084, children: 0.33 +/- 0.17, P=0.0048) and decreased sTNF-R1/R2 ratio (adults: mean +/- SD=0.96 +/- 0.73, children: 2.85 +/- 2.06 vs. adults: 4.82+/-3.40, P=0.0272, children: 4 42 +/- 2 30, P=0.0167) were measured in patients with bronchial hyperreactivityThe provocation doses of methacholine causing a 20% reduction (PD20) in forced expiratory volume in 1 sec (FEV1) were found to be in a significant negative linear correlation with TNFalpha sTNF-R1 and R2 levels in hyperreactive adults and with TNFalpha, sTNF-R2 in hyperreactive children. TNFalpha correlated significantly with its receptors both in hyperreactive adults and children and with the body mass index (BMI) values of adults. The TNF system may contribute to the pathophysiology of bronchial hyperreactivity Altered shedding of sTNF-R1 seems to occur in hyperreactive patients.
Halász
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A
1st Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Cserháti
E
E
Magyar
R
R
Kovács
M
M
Cseh
K
K
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D015703:Antigens, CD; D016085:Bronchoconstrictor Agents; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride