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

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

^* To whom correspondence should be addressed. E-mail: prmrocco{at}biof.ufrj.br.

	Abstract

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

One hundred and twenty BALB/c mice were randomly divided into 5 groups. In control group saline was intratracheally (i.t.) instilled. In ALI group mice received E. coli lipopolysaccharide (10 µg, i.t.). ALI animals were further randomized into 4 subgroups to receive: saline (0.1 ml i.v.) or methylprednisolone (2 mg·kg^-1 i.v.) at 6 h, 24 h or daily (during 7 days, beginning at day 1). At one, three and eight 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 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 ALI.