Document 0508
 DOCN  M9590508
 TI    Corticosteroids class-dependently inhibit in vitro Th1- and Th2-type
       cytokine production.
 DT    9509
 AU    Snijdewint FG; Kapsenberg ML; Wauben-Penris PJ; Bos JD; Department of
       Dermatology, University of Amsterdam, The; Netherlands.
 SO    Immunopharmacology. 1995 Mar;29(2):93-101. Unique Identifier : AIDSLINE
       MED/95293643
 AB    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.
 DE    Adrenal Cortex Hormones/CLASSIFICATION/*PHARMACOLOGY  Animal
       Clobetasol/ANALOGS & DERIVATIVES/PHARMACOLOGY  Cytokines/*BIOSYNTHESIS
       Drug Interactions  Human  Hydrocortisone/ANALOGS &
       DERIVATIVES/PHARMACOLOGY  In Vitro  Interferon Type II/BIOSYNTHESIS
       Interleukin-2/BIOSYNTHESIS/PHARMACOLOGY  Interleukin-4/BIOSYNTHESIS
       Lymphocyte Transformation/DRUG EFFECTS  Mice
       Pregnenediones/PHARMACOLOGY  Receptors, Interleukin-2/BIOSYNTHESIS
       Support, Non-U.S. Gov't  Th1 Cells/*DRUG EFFECTS/IMMUNOLOGY  Th2
       Cells/*DRUG EFFECTS/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).