Serum concentration and circadian profiles of cathepsins B, H and L, and their inhibitors, stefins A and B, in asthma

Background: In order to determine the effect of asthma on serum concentrati ons of cathepsins B, H and L, and stefins A and B, the circadian and concen tration profiles were followed in steroid-independent and steroid-dependent asthmatics before and after I-week treatment with methylprednisolone and c yclosporin A. Methods: Serum samples were taken at 4-h intervals throughout a 24-h period. Cathepsin and stefin concentrations were assayed using spec ific ELISAs. Data were analysed by one-way ANOVA and least squares fit of 2 4-h cosine. Results: Temporal analysis of these proteins revealed little or no significant changes with time over a 24-h period. In comparison to norm al sera, cathepsin H concentrations were elevated in all asthmatic patients , concentrations of both stefins were decreased in steroid-independent asth matics, and stefin A concentrations were increased in steroid-dependent ast hmatics before therapy. The effect of methylprednisolone treatment was demo nstrated on decreased cathepsin B and increased cathepsin L concentrations in post-therapy serum samples. On the other hand, cyclosporin A treatment l ed to increased concentrations of cathepsins H and L. However, concentratio ns of stefins A and B were unaffected. Conclusions: This study associated a lterations in balance of serum cysteine proteinases and their inhibitors in asthmatic patients, which has raised the possibility of their involvement in asthma pathogenesis. Validated rhythms of cathepsins and stefins in asth matic sera exhibited temporal differences, which are too small to influence the time of sampling for their quantitative measurement over the course of a day. (C) 2001 Elsevier Science B.V. All rights reserved.