       Document 0465
 DOCN  M9460465
 TI    Blood lymphocytes of autoimmune disease patients receiving FK506 exhibit
       normal ex vivo cytokine gene expression and proliferative responses.
 DT    9404
 AU    Lemster B; Woo J; Thomson AW; Department of Surgery, University of
       Pittsburgh Medical Center,; PA 15213.
 SO    Immunol Lett. 1993 Nov;38(3):179-83. Unique Identifier : AIDSLINE
       MED/94171282
 AB    It is well recognized that FK506 (Tacrolimus) is a powerful inhibitor of
       CD4+ T-cell activation and proliferation in vitro. In this study,
       immunophenotypic and functional analyses were performed on peripheral
       blood mononuclear cells from a total of 30 patients with various
       autoimmune disorders before and whilst the patients were receiving
       systemic FK506 therapy. The expression of cell surface IL-2R alpha and
       -beta on CD4+ and CD8+ cells, cytokine message (IL-2, IFN-gamma, IL-4,
       IL-10) and the proliferative activity of lymphocytes in response to
       rIL-2 were examined. Despite plasma levels of FK506 compatible with the
       blockade of IL-2 production by stimulated T cells in vitro, cells from
       patients on FK506 treatment cultured ex vivo with either ConA or IL-2
       did not differ from normal cells in their expression of cytokine mRNA or
       their proliferative responses. These data indicate that the presumed in
       vivo suppression of T-cell function by FK506 is rapidly reversible ex
       vivo. Alternatively/additionally, they suggest that FK506 may mediate
       its in vivo action primarily by mechanisms other than blockade of T-cell
       function.
 DE    Adolescence  Adult  Aged  Antigens, CD8/BLOOD  Autoimmune Diseases/DRUG
       THERAPY/*IMMUNOLOGY  Cytokines/*DRUG EFFECTS  CD4-CD8 Ratio/DRUG EFFECTS
       Female  FK-506/*PHARMACOLOGY  Gene Expression/DRUG EFFECTS  Human
       Interleukin-2  Lymphocyte Transformation/DRUG EFFECTS  Male  Middle Age
       Polymerase Chain Reaction  T-Lymphocytes/*DRUG EFFECTS  T4
       Lymphocytes/DRUG EFFECTS  JOURNAL ARTICLE

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

