Human recombinant interferon-alpha2a and interferon-alphaA/D have different effects on bleomycin-induced lung injury.
BACKGROUND
Bleomycin (Bleo)-induced lung injury in mice serves as an animal model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains unclear, but it comprises both inflammatory and fibrotic components. The cytokine interferon (IFN)-alpha is produced by macrophages and may modulate both fibrogenesis and the determination of T lymphocyte phenotype in pulmonary fibrosis.


OBJECTIVE
To investigate the effect of two preparations of recombinant IFN-alpha (IFN-alphaA/D and IFN-alpha2a) on Bleo-induced lung injury in C57BL/6 mice.


METHODS
Mice were treated by a single intratracheal (IT) instillation of 0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN-alpha preparations, IFN-alphaA/D or IFN-alpha2a in saline, or saline alone were administered by daily intraperitoneal injections starting 1 day prior to IT instillation. The treatment groups were as follows: IT Bleo and intraperitoneal saline; IT Bleo and intraperitoneal IFN-alpha2a; IT Bleo and intraperitoneal IFN-alphaA/D; IT saline and intraperitoneal IFN-alphaA/D or IFN-alpha2a; IT saline and intraperitoneal saline. The animals were sacrificed 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity and fibrosis fraction and by biochemical analysis of lung hydroxyproline content.


RESULTS
In Bleo-treated mice, IFN-alpha2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury.


CONCLUSIONS
IFN-alpha may enhance Bleo-induced lung injury but this effect varies with different IFN preparations.
Berkman
N
N
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem, Israel. Neville@lung.hadassah.org.il
Kremer
S
S
Or
R
R
Lossos
I S
IS
Christensen
T G
TG
Goldstein
R H
RH
Breuer
R
R
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D001761:Bleomycin