Effect of immunomodulators on bleomycin-induced lung injury.
BACKGROUND
The role of lymphocytes and their subpopulations in lung fibrosis is as yet unclear.


OBJECTIVE
To define the role of immunomodulation in bleomycin-induced inflammatory fibrotic lung injury, by testing the effect of two known Th1 inhibitors: linomide and pentoxifylline.


METHODS
C57BL/6 mice were treated by a single intratracheal instillation of 0.06 mg bleomycin in 0.01 ml saline or saline alone. Treatment groups included: (1) intratracheal bleomycin and daily treatment with linomide or pentoxifylline; (2) intratracheal bleomycin and daily water; (3) intratracheal saline and daily linomide or pentoxifylline; (4) intratracheal saline and daily water. Linomide and pentoxifylline were available per os in the drinking water from 1 day prior to intratracheal instillation. Animals were studied 14 days after intratracheal instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity, fibrosis fraction and alveolar wall area fraction, and by biochemical analysis of lung hydroxyproline content.


RESULTS
Linomide or pentoxifylline did not cause any lung injury in saline-treated control mice. Overt signs of lung injury were apparent in bleomycin-treated mice. These changes were not affected by daily treatment with linomide or pentoxifylline, which were given in the highest tolerable dose.


CONCLUSIONS
This study does not support the use of linomide or pentoxifylline to prevent or ameliorate lung fibrosis and may suggest that drug-induced differentiation of T lymphocytes into Th1/th2 subpopulations does not affect the evolution of bleomycin-induced lung injury.
Kremer
S
S
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Breuer
R
R
Lossos
I S
IS
Berkman
N
N
Christensen
T G
TG
Connor
M W
MW
Goldstein
R H
RH
Or
R
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D006912:Hydroxyquinolines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010431:Pentoxifylline / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D006912:Hydroxyquinolines; D001761:Bleomycin; C045282:roquinimex; D010431:Pentoxifylline