Lymphoblastosis inhibition and plaque-forming cell response of several anti-inflammatory steroids in mice

Abstract

Anti-inflammatory glucocorticoid (GC) derivatives have been clinically used in immune-malfunctional diseases for their immunosuppressive activity. However, there is still a lack of knowledge on the relationship between anti-inflammatory and immuno-suppressive activities. In order to compare immunosuppressive activities with the known anti-inflammatory activities of the GC derivatives, eight clinically used GC derivatives including hydrocortisone, prednisolone, 6α-methyl prednisolone, triamcinolone, dexamethasone, betamethasone, triamcinolone acetonide and fluocinolone acetonide were selected, and lymphoblastosis inhibition and plaque-forming cell (PFC) response in mice were studied as immunological parameters. In Con A-induced lymphoblastosis inhibitionin vitro, all derivatives showed potent inhibition. IC50 values of the derivatives except methyl prednisolone and triamcinolone were less than 10−7M and good dose dependency was obtained. This result was well correlated with that of their anti-inflammatory potencies and their receptor binding affinities. However, in PFC response, consistent results were not obtained. Total numbers of PFCs per spleen were decreased by some derivatives, but numbers of PFCs per 106 cells were not decreased by systemic administration of GC at the dose of 0.05 mg/mouse. Furthermore, at the dose of 0.1 mg/mouse, numbers of PFCs per 106 cells were found to be increased, although total PFCs per spleen were decreased.