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Departments of
*
Medicine and
Pathology, Northwestern University Medical School, Chicago, IL 60611;
Institute of Medical Science, University of Tokyo, Tokyo, Japan; and
Veterans Administration, Lakeside Division, Chicago Health Care System, Chicago IL 60611
IL-4 is a cytokine with anti-inflammatory properties on
activated macrophages. Rheumatoid arthritis, an autoimmune inflammatory
disease, is characterized by a paucity of IL-4 and an abundance of
synovial macrophage-derived mediators. Herein, the effect of a single
injection of adenovirus-producing rat IL-4 (AxCAIL-4) or a control
virus with no inserted gene was compared with the effect of PBS
injection into rat ankles. Ankles were injected before arthritis onset
or at maximal inflammation. Preventatively, AxCAIL-4 reduced
adjuvant-induced arthritis (AIA)- and/or AIA/adenoviral-induced ankle
inflammation, decreasing articular index scores, ankle circumferences,
paw volumes, radiographic scores, mean levels of monocyte
chemoattractant protein-1, the number of inflammatory cells, and the
number of synovial blood vessels. Therapeutically, AxCAIL-4 also
decreased ankle circumferences and paw volumes in comparison with a
control virus with no inserted gene and PBS groups. After arthritis
onset, mean levels of TNF-
, IL-1
, macrophage inflammatory
protein-2, and RANTES were decreased in AxCAIL-4 rat ankle homogenates
compared with PBS-treated homogenates. Thus, increased expression of
IL-4 via gene therapy administered in a preventative and/or therapeutic
manner reduced joint inflammation, synovial cellularity, levels of
proinflammatory cytokines, vascularization, and bony destruction in rat
AIA, suggesting that a similar treatment in humans may be
beneficial.
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