A cellular abnormality in glucocorticoid resistant asthma

Abstract

Peripheral blood mononuclear cells from asthmatic patients were cultured in soft agar with or without the synthetic glucocorticoid methylprednisolone (MP). The resulting colonies consisted mostly of T lymphocytes but included monocytes, often in a central position. Colony growth from patients whose asthma had responded satisfactorily to glucocorticoid medication was inhibited by MP in vitro at concentrations as low as 10(-9) M, and the ratio of helper to suppressor/cytotoxic T cells was reduced relative to untreated cultures. In contrast, patients shown to be resistant to the therapeutic effects of glucocorticoids yield colonies which differed little in number, size or constituent phenotype, whether untreated or exposed to MP at concentrations as high as 10(-8) M. Higher concentrations inhibited colony growth from both types of patient. Hybrid colonies were generated from partially purified cells from pairs of patients: monocytes from one member and lymphocytes from the other. The steroid sensitivity of these colonies was found to be dependent upon the source of the monocytes and not the lymphocytes. The results support the view that, in glucocorticoid resistant asthma, there is a defect in monocyte responsiveness to the hormone. This defect could explain the poor therapeutic effect of glucocorticoids in these patients. The results suggest that monocyte factors may be of importance in the pathogenesis of asthma in general.