Resistance to Methylprednisolone in Cultures of Blood Mononuclear Cells from Glucocorticoid-Resistant Asthmatic Patients

Abstract

1. In order to investigate the cellular mechanism of glucocorticoid resistance in chronic asthma, peripheral blood mononuclear cells (MNC) from asthmatic patients were cultured in soft agar. 2. Cells from patients known to be clinically sensitive to glucocorticoid therapy did not differ significantly from those of clinically resistant patients in terms of their immunophenotype or the number of colonies generated by culture in the presence of phytohaemagglutinin. 3. The glucocorticoid methylprednisolone (MP) at low concentration (10 nmol/l) inhibited colony growth from cells of glucocorticoid-sensitive patients, whereas there was much less inhibition of colony growth from resistant patients' cells. 4. In a small prospective study inhibition of colony growth by methylprednisolone in vitro correlated with the subsequently determined sensitivity of the patients' asthma to glucocorticoid therapy. 5. Assessment in vitro of glucocorticoid sensitivity may help to predict which patients may be spared ineffectual glucocorticoid medication. The results raise the possibility that peripheral blood mononuclear cells may respond to glucocorticoid in a similar manner to cells involved in the pathogenesis of asthma.