Differential potency of beclomethasone esters in-vitro on human T-lymphocyte cytokine production and osteoblast activity

Beclomethasone dipropionate is an inhaled corticosteroid, used for the trea tment of asthma. It is metabolised to 17-beclomethasone monopropionate, whi ch has greater affinity for corticosteroid receptors than the parent compou nd, and to beclomethasone. We investigated the potency of beclomethasone di propionate, 17-beclomethasone monopropionate and beclomethasone (compared w ith dexamethasone as a reference steroid) in two different human cell types , peripheral blood mononuclear cells and osteoblasts. We found that beclomethasone dipropionate, 17-beclomethasone monopropionate (EC50 10(-14) M) and beclomethasone (EC50 approx. 10(-12) M) were much mor e potent than dexamethasone (EC50 10(-8) M) in inhibiting interleukin-5 pro duction by peripheral blood mononuclear cells. In contrast, beclomethasone dipropionate, 17-beclomethasone monopropionate and beclomethasone were equi potent with dexamethasone (EC50 range 0.3- 1.2 x 10(-9) M) in affecting sev eral functional assays of osteoblasts (e.g. alkaline phosphatase activity a nd osteocalcin synthesis). These results show that the relative bioactivities of corticosteroids vary between different human cell types, and that affinities observed in recepto r binding assays are not necessarily predictive of the bioactivity in cell populations, such as peripheral blood mononuclear cells and osteoblasts, wh ich are putatively relevant to efficacy and side effects respectively.