Open AccessAdrenalectomy permits a late, local TNF‐α release in LPS‐challenged rat airways
Author(s) -
MillerLarsson A.,
Runström A.,
Brattsand R
Publication year - 1999
Publication title -
european respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.021
H-Index - 241
eISSN - 1399-3003
pISSN - 0903-1936
DOI - 10.1034/j.1399-3003.1999.13f15.x
Subject(s) - endogeny , lipopolysaccharide , tumor necrosis factor alpha , medicine , endocrinology , adrenalectomy , corticosterone , cytokine , peripheral blood mononuclear cell , necrosis , inflammatory response , glucocorticoid , inflammation , chemistry , in vitro , hormone , biochemistry
The normal rise of circulating endogenous glucocorticosteroids (GCS), in response to immunological stimuli, can be impaired in patients with inflammatory diseases. The aim of this study was to investigate whether abolition of the endogenous GCS response promotes local production of the pro‐inflammatory cytokine, tumour necrosis factor (TNF)‐α, in challenged airways and affects the cellular response in rats. In adrenalectomized or sham operated rats, the trachea and main bronchi were lavaged at various times after intratracheal instillation of low dose lipopolysaccharide (LPS). TNF‐α in lavage fluid and plasma corticosterone were measured, and cells were differentiated. In adrenalectomized rats, LPS‐induced in the airways a biphasic TNF‐α release peaking at 2 and 6 h, whereas in sham operated rats the second peak was absent; probably inhibited by the strong rise of plasma corticosterone. The second peak was abolished in adrenalectomized rats by pretreatment with exogenous GCS. The LPS‐induced neutrophil influx and a decrease in mononuclear cells were prolonged in adrenalectomized rats. In conclusion, abolition of the endogenous glucocorticosteroid response promotes the late release of tumour necrosis factor‐α in the airways and prolongs the cellular response. This suggests that a normal rise of endogenous glucocorticosteroid after an immunological trigger contributes to a dampening of the late inflammatory activity.