Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice.
OBJECTIVE
Corticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise.


METHODS
Prospective, randomized, controlled experimental study.


METHODS
University research laboratory.


METHODS
One hundred twenty-eight BALB/c mice (20-25 g).


METHODS
Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Cexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 microg, ALIp) or intraperitoneally (125 microg, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively).


RESULTS
At 24 hrs, lung static elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interleukin-6, and transforming growth factor (TGF)-beta levels in bronchoalveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta1 and TGF-beta2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFNgamma, and TGF-beta2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups.


CONCLUSIONS
Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.
Leite-Junior
José Henrique P
JH
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Brazil.
Garcia
Cristiane S N B
CS
Souza-Fernandes
Alba B
AB
Silva
Pedro L
PL
Ornellas
Debora S
DS
Larangeira
Andrea P
AP
Castro-Faria-Neto
Hugo C
HC
Morales
Marcelo M
MM
Negri
Elnara M
EM
Capelozzi
Vera L
VL
Zin
Walter A
WA
Pelosi
Paolo
P
Bozza
Patricia T
PT
Rocco
Patricia R M
PR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D024022:Fibrillar Collagens / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008775:Methylprednisolone / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D001261:Pulmonary Atelectasis / Q000473:pathology; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D024022:Fibrillar Collagens; D018836:Inflammation Mediators; D008775:Methylprednisolone