       Document 0527
 DOCN  M9620527
 TI    Elevated Th1- or Th0-like cytokine mRNA in peripheral circulation of
       patients with rheumatoid arthritis. Modulation by treatment with
       anti-ICAM-1 correlates with clinical benefit.
 DT    9602
 AU    Schulze-Koops H; Lipsky PE; Kavanaugh AF; Davis LS; University of Texas
       Southwestern Medical Center, Harold C.; Simmons Arthritis Research
       Center, Department of Internal; Medicine, Dallas, TX 75235, USA.
 SO    J Immunol. 1995 Nov 15;155(10):5029-37. Unique Identifier : AIDSLINE
       MED/96062327
 AB    The current studies examined whether cytokine patterns indicative of an
       imbalance in Th1 and Th2 cells could be identified in PBMC of patients
       with active rheumatoid arthritis (RA). To investigate this possibility,
       a reproducible PCR technique to assess cytokine mRNA levels in PBMC was
       employed that minimized in vitro manipulation of the cells. Seven of 14
       RA patients had increased mRNA levels for IL-2, 5/14 for IFN-gamma, 3/14
       for IL-4, and 4/14 for the IL-2R alpha-chain, compared with normal
       donors. Whereas 4 patients had elevated mRNA for IL-2 and IFN-gamma,
       indicative of an increase in activated Th1 or Th0 cells, 1 of 14
       patients expressed low levels of IL-2 and IFN-gamma and high levels of
       IL-4 mRNA. Seven RA patients were treated with a mAb to ICAM-1 (CD54).
       To determine whether changes in cytokine mRNA levels might be associated
       with and/or account for the anti-inflammatory effect of anti-ICAM-1 mAb
       therapy, changes in cytokine mRNA levels were assessed and correlated
       with clinical improvement. Anti-ICAM-1 mAb administration was followed
       by a prompt and transient increase of IFN-gamma mRNA. Elevation of
       IFN-gamma mRNA expression throughout the treatment period reflected a
       temporary increase in the number of circulating CD3+CD4+ T cells,
       suggestive of altered circulatory patterns of activated Th1-like cells
       and was related to clinical efficacy. The results indicate that elevated
       cytokine mRNA levels characteristic for Th1 cells can be detected in the
       PBMC in active RA and, furthermore, that anti-ICAM-1 mAb may be
       beneficial in RA by altering the recruitment of activated Th1-like cells
       into the synovium. This assumption further strengthens the hypothesis of
       a significant contribution of Th1-like cells to the pathogenesis of RA.
 DE    Antibodies/THERAPEUTIC USE  Arthritis, Rheumatoid/BLOOD/DRUG
       THERAPY/*IMMUNOLOGY  Base Sequence  Cells, Cultured  Cytokines/*BLOOD
       Human  Intercellular Adhesion Molecule-1/*IMMUNOLOGY  Interferon Type
       II/IMMUNOLOGY  Leukocytes, Mononuclear/IMMUNOLOGY  Molecular Sequence
       Data  RNA, Messenger/*BLOOD  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Th1 Cells/*IMMUNOLOGY  JOURNAL ARTICLE

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

