The effects of hydrocortisone on in vitro lymphocyte proliferation and interleukin-2 and -4 production in corticosteroid sensitive and resistant subjects.
Corticosteroids (CS) are potent immunosuppressive and anti-inflammatory agents which are frequently used to treat a number of conditions such as rheumatoid arthritis (RA), asthma, and renal allograft rejection. Patients taking corticosteroids can be divided into 'steroid-sensitive' (SS) and 'resistant' (SR) groups on clinical and laboratory criteria. Corticosteroid 'resistance' has been extensively documented in asthma and renal allografting. The underlying mechanisms are unknown. Using the inhibition by hydrocortisone of concanavalin-A induced lymphocyte proliferation in vitro, we have divided rheumatoid arthritis patients (RA) and normal controls (HC) into SS and SR groups. The SS and SR phenotypes were stable over several months in RA and HC subjects. Inhibition of Con-A induced production of interleukin-2 and -4 by corticosteroids in vitro correlated with the in vitro defined SS and SR phenotype. When highly purified T-cells were stimulated via the CD3 and CD28 receptor pathways, corticosteroids did not inhibit cell proliferation in SS and ST subjects. It may be concluded that the SS and SR phenomenon is a stable intrinsic property of the individual which is dependent primarily on the inhibitory effects of corticosteroids on accessory cell function and only secondarily on T-cell function. This is a novel observation for the inhibitory effects of corticosteroids on T-lymphocytes.
Chikanza
L C
LC
Rheumatology Unit, United Medical School, Guy's Hospital, London, UK.
Panayi
G S
GS
D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D004351:Drug Resistance; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*
D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D015847:Interleukin-4; D006854:Hydrocortisone