INDUCTION OF HUMAN AIRWAY HYPERRESPONSIVENESS BY TUMOR-NECROSIS-FACTOR-ALPHA

Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogen esis of asthma; however, little is known of its direct effect on smoot h muscle reactivity. We investigated the effect of TNF alpha on the re sponsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased responsiveness to electrical fiel d stimulation (113 +/- 8, 110 +/- 4 and 112 +/- 2% respectively) compa red to control (99 +/- 2%) (P < 0.05, n = 6). Responses were not incre ased in sensitized tissue (101 +/- 3% versus 105 +/- 5%, n = 3, P > 0. 05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%, n = 3, P = 0.38). These results show that TNF alpha causes an increase in responsiveness of human bronchial tissue and that this oc curs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiven ess.