Sz. Anticevich et al., INDUCTION OF HUMAN AIRWAY HYPERRESPONSIVENESS BY TUMOR-NECROSIS-FACTOR-ALPHA, European journal of pharmacology, 284(1-2), 1995, pp. 221-225
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.