Corticosteroids class-dependently inhibit in vitro Th1- and Th2-type cytokine production.
Corticosteroids (CS) are very potent immunosuppressive agents and are widely used to treat inflammatory diseases. On the basis of their clinical efficacy and potency CS have been divided into different classes. In the present study we investigated whether the class-associated effects of CS are correlated with a differential in vitro effect on cytokine production by T lymphocytes. Therefore, we determined the in vitro effects of CS on the production of Th1- and Th2-type cytokines. The addition of CS, in the range of 10(-9) to 10(-4) M, resulted in a class- and dose-dependent inhibition of the production of both IFN-gamma and IL-4. Notably, at the lowest doses tested, hydrocortisone and hydrocortisone 17-butyrate had a stimulatory effect on IL-4 production. CS class-dependently inhibited the IL-2 production by T cells but did not affect IL-2R expression of the T cells. Addition of rIL-2 could not completely restore the inhibitory effect of the CS on proliferation and on IFN-gamma and IL-4 production, indicating that CS act only partially via inhibition of IL-2 production. The demonstrated positive correlation between the clinical efficacy and the in vitro effects of the different classes of CS strongly suggests that the effect of CS on T-cell-mediated inflammation follows from inhibition of proliferation and cytokine production by T lymphocytes. The in vitro method used will be valuable for investigating and classifying new types of CS and other substances for applications in T-cell-mediated diseases.
Snijdewint
F G
FG
Department of Dermatology, University of Amsterdam, The Netherlands.
Kapsenberg
M L
ML
Wauben-Penris
P J
PJ
Bos
J D
JD
D000305:Adrenal Cortex Hormones / Q000145:classification / Q000494:pharmacology*; D000818:Animals; D019819:Budesonide; D002990:Clobetasol / Q000031:analogs & derivatives / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004347:Drug Interactions; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D011282:Pregnenediones / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007376:Interleukin-2; D011282:Pregnenediones; D015375:Receptors, Interleukin-2; C007975:hydrocortisone-17-butyrate; D015847:Interleukin-4; D019819:Budesonide; D007371:Interferon-gamma; D002990:Clobetasol; D006854:Hydrocortisone