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Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury

¹ Laboratory of Pulmonary Investigation, ² Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, ⁴ Laboratory of Immunopharmacology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, ³ Dept of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil, and ⁵ Dept of Ambient, Health and Safety, University of Insubria, Varese, Italy.

CORRESPONDENCE: P. R. M. Rocco, Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil. Fax: 55 2122808193. E-mail: prmrocco{at}biof.ufrj.br

Keywords: Acute lung injury, collagen, corticosteroid, elastance, lung histology, matrix metalloproteinase

Received: April 5, 2008
Accepted September 27, 2008

The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI).

In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 µg i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg·kg^–1 i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured.

In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design.

Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.