Immunosuppressive activity of prednisone and prednisolone and their metabolic interconversion in the mixed lymphocyte reaction.
The immunosuppressive activities of prednisolone, prednisone and cortisol were assessed and compared using a modified micro-2-way mixed lymphocyte reaction (MLR) assay. As measured by the inhibition of the MLR on day 3, prednisolone was 2.40 +/- 0.98 times more potent than cortisol: The average EC50S for prednisolone and cortisol were 28.25 +/- 7.8 ng/ml and 63.25 +/- 16.88 ng/ml, respectively. Prednisone (10 - 1000 ng/ml) had little or no immunosuppressive activity and did not affect the inhibition due to prednisolone or cortisol. Although, prednisone was inactive in the MLR, it was slowly being converted to prednisolone by 11-hydroxylation. MLR cultures with starting prednisone concentrations of 100, 200, 500, 1000 and 2000 ng/ml, contained 28, 34, 46, 50 and 81 ng/ml of prednisolone, respectively, on day 3 of the culturing period. The reverse reaction, the conversion of prednisolone to prednisone, did not occur. The inactivity of prednisone despite a significant conversion to its biologically active 11-hydroxyl metabolite, prednisolone, suggests the importance of the duration and timing of prednisolone's presence to immunosuppressive activity in the MLR culture.
Tsang
S Y
SY
Garovoy
M R
MR
Benet
L Z
LZ
D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D011239:Prednisolone / Q000378:metabolism / Q000494:pharmacology*; D011241:Prednisone / Q000378:metabolism / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D011239:Prednisolone; D011241:Prednisone; D006854:Hydrocortisone