       Document 0980
 DOCN  M9650980
 TI    Nonsteroidal anti-inflammatory drugs differentially regulate cytokine
       production in human lymphocytes: up-regulation of TNF, IFN-gamma and
       IL-2, in contrast to down-regulation of IL-6 production.
 DT    9505
 AU    Tsuboi I; Tanaka H; Nakao M; Shichijo S; Itoh K; Department of
       Immunology, Kurume University School of Medicine,; Japan.
 SO    Cytokine. 1995 May;7(4):372-9. Unique Identifier : AIDSLINE MED/96172549
 AB    Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known as
       immunoregulators, but the mechanisms of their action are not fully
       explained by the inhibition of PG synthesis. We have investigated the
       effect of NSAIDs on cytokine production in human PBMC and T cell clones
       (TCC). NSAIDs up-regulated TNF, IFN-gamma and IL-2 production at both
       the mRNA and protein levels, and IL-12 expression at the mRNA level. In
       contrast, NSAIDs down-regulated IL-6 production both at the mRNA and
       protein levels, and down-regulated IL-4 mRNA expression. The modulation
       at the mRNA level became detectable 1 h after culture. This modulation
       was also observed at the level of TCC. Indomethacin (IM) enhanced TNF
       production in all the eight TCC that were established from a patient
       with human T lymphotrophic virus type 1 uveitis or pulmonary
       sarcoidosis, and suppressed IL-6 production in six of the eight TCC,
       without affecting their low levels of PGE2 production. IM also enhanced
       TNF and suppressed IL-6 production, respectively, in both IL-2-activated
       PBMC and IL-2-dependent NK cell line, with the inhibition of their high
       levels of PGE2 production. Culture with PGE2 alone suppressed TNF
       production by three of the six TCC and NK cell lines, which was
       neutralized by addition of IM. It had, however, no effect on TNF
       production by the remaining three TCC or IL-2-activated PBMC. The
       effects of PGE2 on IL-6 production also varied among TCC.(ABSTRACT
       TRUNCATED AT 250 WORDS)
 DE    Anti-Inflammatory Agents, Non-Steroidal/*PHARMACOLOGY  Base Sequence
       Cells, Cultured  Clone Cells/DRUG EFFECTS/METABOLISM
       Diclofenac/PHARMACOLOGY  Dinoprostone/BIOSYNTHESIS/GENETICS  Gene
       Expression Regulation/*DRUG EFFECTS  Human  HTLV-I Infections/PATHOLOGY
       Indomethacin/PHARMACOLOGY  Interferon Type II/*BIOSYNTHESIS/GENETICS
       Interleukin-2/*BIOSYNTHESIS/GENETICS
       Interleukin-6/*BIOSYNTHESIS/GENETICS  Ketoprofen/PHARMACOLOGY  Leukemia,
       T-Cell, Acute/PATHOLOGY  Leukocytes, Mononuclear/*DRUG
       EFFECTS/METABOLISM  Lymphocyte Transformation  Molecular Sequence Data
       Polymerase Chain Reaction  RNA, Messenger/BIOSYNTHESIS/GENETICS
       Sarcoidosis, Pulmonary/PATHOLOGY  T-Lymphocyte Subsets/DRUG
       EFFECTS/METABOLISM  Th1 Cells/*DRUG EFFECTS/METABOLISM  Th2 Cells/*DRUG
       EFFECTS/METABOLISM  Tumor Cells, Cultured  Tumor Necrosis
       Factor/BIOSYNTHESIS/GENETICS  Uveitis/PATHOLOGY/VIROLOGY  JOURNAL
       ARTICLE

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

