In vitro study of regulation of IL-6 production in bronchiectasis.
Persistent airway inflammation is an important pathogenetic factor in bronchiectasis, and interleukin (IL)-6 is among the mediators implicated in regulation of inflammation in bronchiectatic airways. We postulated that airway secretion with its constituents of cytokines and enzymes would provide an environment for perpetuation of inflammation in vivo. We aimed to determine the action of sputum from patients with bronchiectasis on IL-6 production from cultured normal human bronchial epithelial (NHBE) cells and its modulation by anti-inflammatory drugs in vitro. Cultures of NHBE cells were tested with (i) sputum of bronchiectatic patients, (ii) anti-tumor necrosis factor-alpha (TNF-alpha) pre-treated sputum, or (iii) recombinant human (rh)-TNF-alpha. Alternatively, NHBE cells were incubated with one of the anti-inflammatory drugs before treatment with sputum or rh-TNF-alpha. IL-6 produced into the medium was assayed by ELISA. Sputum in bronchiectasis stimulated IL-6 production from NHBE cells by 1.9 times. This was largely attributable to TNF-alpha as pre-incubation of sputum sol with anti-TNF-alpha almost neutralized the sputum effect. Apart from dexamethasone, the other drugs exerted inhibitory effects on IL-6 production. Ibuprofen suppressed sputum-stimulated IL-6 production to levels above control and effect levelled off at 50-100 microg/mi, contrasting the dose-dependent suppression to control level with MK-663 (0.1-10 microg/ml) and to sub-control levels with triptolide (20-1000 ng/ml). Our results support that sputum in bronchiectasis can stimulate IL-6 production from NHBE cells, and TNF-alpha is an important cytokine mediating the process. The suppressive effects observed with ibuprofen, triptolide and MK-663 warrant further study.
Ho
James C
JC
Division of Respiratory and Critical Care Medicine, University Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China.
Tipoe
George
G
Zheng
L
L
Leung
T M
TM
Tsang
Kenneth W T
KW
Shum
Daisy K Y
DK
Lau
C S
CS
Mak
Judith C W
JC
Lam
W K
WK
Ip
Mary S M
MS
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001987:Bronchiectasis / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D013183:Sputum / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha