Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice

Abstract

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.

Design: Prospective, randomized, controlled experimental study.

Setting: University research laboratory.

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

Interventions: 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).

Measurements and main 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.