Fluticasone, but not salmeterol, reduces cigarette smoke-induced production of interleukin-8 in human airway smooth muscle.
Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease. We have recently shown that cigarette smoke extract synergises with tumour necrosis factor alpha (TNFalpha) in the induction of interleukin-8 (IL-8) from human airway smooth muscle cells. We have investigated the effect of fluticasone propionate, a corticosteroid, and salmeterol, a beta 2-adrenergic receptor agonist, on cigarette smoke extract-induced IL-8 production by human airway smooth muscle cells. Human airway smooth muscle cells in primary culture were exposed to cigarette smoke extract and/or TNFalpha (1 ng ml(-1)) with and without pretreatment with fluticasone (10(-13)-10(-8)M) and/or salmeterol (10(-11)-10(-6)M). IL-8 was analysed by ELISA. Fluticasone dose-dependently inhibited IL-8 release induced by cigarette smoke extract, TNFalpha or combined cigarette smoke extract and TNFalpha. However, while IL-8 release in the presence of cigarette smoke extract alone was completely inhibited by fluticasone, IL-8 production induced by cigarette smoke extract and TNFalpha was only partially reduced. Salmeterol alone had no effect on cigarette smoke extract and/or TNFalpha-induced IL-8 production from human airway smooth muscle cells. Combined fluticasone and salmeterol did not cause further inhibitory effects compared to fluticasone alone. Fluticasone but not salmeterol is effective in reducing cigarette smoke extract-induced IL-8 production in human airway smooth muscle cells. The reduced inhibition of cigarette smoke extract- and TNFalpha-induced IL-8 release by fluticasone may explain why corticosteroids are less effective in chronic obstructive pulmonary disease where increased amounts of TNFalpha are present.
Oltmanns
Ute
U
Experimental Studies, National Heart & Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.
Walters
Matt
M
Sukkar
Maria
M
Xie
Sherry
S
Issa
Razao
R
Mitchell
Jane
J
Johnson
Malcolm
M
Chung
Kian Fan
KF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000068298:Fluticasone; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000068299:Salmeterol Xinafoate; D012906:Smoke; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D005938:Glucocorticoids; D016209:Interleukin-8; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol