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 treatment of asthma. It is metabolised to 17-beclomethasone monopropionate, which has greater affinity for corticosteroid receptors than the parent compound, and to beclomethasone. We investigated the potency of beclomethasone dipropionate, 17-beclomethasone monopropionate and beclomethasone (compared with 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 more potent than dexamethasone (EC50 10(-8) M) in inhibiting interleukin-5 production by peripheral blood mononuclear cells. In contrast, beclomethasone dipropionate, 17-beclomethasone monopropionate and beclomethasone were equipotent with dexamethasone (EC50 range 0.3-1.2 x 10(-9) M) in affecting several functional assays of osteoblasts (e.g. alkaline phosphatase activity and osteocalcin synthesis). These results show that the relative bioactivities of corticosteroids vary between different human cell types, and that affinities observed in receptor binding assays are not necessarily predictive of the bioactivity in cell populations, such as peripheral blood mononuclear cells and osteoblasts, which are putatively relevant to efficacy and side effects respectively.
Seeto
C
C
Department of Pharmacy, Institute of Biomedical Research, University of Sydney, NSW, Australia.
Namkung-Matthai
H
H
Jayrams
S
S
Foe
K
K
Brown
K F
KF
Hughes
J M
JM
Mason
R S
RS
Armour
C L
CL
Seale
J P
JP
D000287:Administration, Topical; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001507:Beclomethasone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004952:Esters; D005938:Glucocorticoids; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004952:Esters; D005938:Glucocorticoids; D015848:Interleukin-5; D015675:Osteocalcin; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D001507:Beclomethasone; D013936:Thymidine