Relationship between the tumor necrosis factor system and the serum interleukin-4, interleukin-5, interleukin-8, eosinophil cationic protein, and immunoglobulin E levels in the bronchial hyperreactivity of adults and their children.

The aim of the study was to investigate the activation of inflammatory mediators interleukin (IL)-4, IL-5, and IL-8; immunoglobulin E (IgE); and eosinophil cationic protein (ECP) and to evaluate the regulatory role of the tumor necrosis system (TNF) system in bronchial hyperreactivity. Adults who had suffered from bronchial asthma in childhood but who had been symptom free for at least 3 years were examined together with their children who did not have asthma. The serum concentrations of TNF-alpha, soluble TNF receptor 1 (sTNF-R1), TNF-R2, IL-4, IL-5, IL-8, ECP, and IgE were studied in symptom-free adults (n = 22) and their children (n = 22) with bronchial hyperreactivity. Nonhyperreactive individuals with a similar medical history (adults, n = 17; children, n = 20) served as controls. Significantly elevated serum TNF-alpha (X +/- SD: 5.13 +/- 1.37 pg/mL versus 3.91 +/- 0.61 pg/mL; p < 0.0001), sTNF-R1 (X +/- SD: 1.37 +/- 0.28 ng/mL versus 1.16 +/- 0.13 ng/mL; p = 0.0002), and sTNF-R2 (X +/- SD: 0.78 +/- 0.42 ng/mL versus 0.43 +/- 0.41 ng/mL; p = 0.0001); IL-4 (X +/- SD: 4.05 +/- 1.02 pg/mL versus 3.34 +/- 0.84 pg/mL; p = 0.0016); IgE (X +/- SD: 390.1 +/- 361.4 KU/L versus 130.2 +/- 166.1 KU/L; p = 0.0001); and ECP (X +/- SD: 17.57 +/- 11.03 micrograms/L versus 10.65 +/- 6.01 micrograms/L; p = 0.0016) concentrations were measured in the subjects with bronchial hyperreactivity as compared with the nonhyperreactive group. Significant positive linear correlations were observed for the bronchial hyperreactive group between the concentrations of TNF-alpha and ECP, TNF-alpha and sTNF-R1, TNF-alpha and IL-8, sTNF-R1 and ECP, sTNF-R1 and IL-8, and sTNF-R2 and IL-8. Moreover, the TNF-alpha and sTNF-R2 levels correlated with the airway reactivity in the hyperreactive group. We suggest that the elevated cytokine levels indicate activation of the immune system in individuals who were previously asthmatic, but recovered, and are now symptom free and in their children with nonasthmatic bronchial hyperreactivity. The TNF system may play a key role in the pathomechanism of bronchial hyperreactivity.