Role of TNF-α and its 55 and 75 kDa receptors in bronchial hyperreactivity

Abstract

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. Serum TNFα and its soluble receptors (sTNF-R1 and R2) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly elevated TNFα (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-RI (adults: 1.44 ± 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 ± 0.40 ng 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 hyperreactivity. The 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 TNFα, sTNF-R1 and R2 levels in hyperreactive adults and with TNFα, sTNF-R2 in hyperreactive children. TNFα 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-RI seems to occur in hyperreactive patients. © 2002 Elsevier Science Ltd.