IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis

IL-4 is a cytokine with anti-inflammatory properties on activated macrophag es. Rheumatoid arthritis, an autoimmune inflammatory disease, is characteri zed by a paucity of IL-4 and an abundance of synovial macrophage-derived me diators. Herein, the effect of a single injection of adenovirus-producing r at IL-4 (AxCAIL-4) or a control virus with no inserted gene was compared wi th the effect of PBS injection into rat ankles, Ankles were injected before arthritis onset or at maximal inflammation. Preventatively, AxCAIL-4 reduc ed adjuvant-induced arthritis (AIA)- and/or AIA/adenoviral-induced ankle in flammation, decreasing articular index scores, ankle circumferences, paw vo lumes, radiographic scores, mean levels of monocyte chemoattractant protein -1, the number of inflammatory cells, and the number of synovial blood vess els. Therapeutically, AxCAIL-4 also decreased ankle circumferences and paw volumes in comparison with a control virus with no inserted gene and PBS gr oups. After arthritis onset, mean levels of TNF-alpha, IL-1 beta, macrophag e inflammatory protein-2, and RANTES were decreased in AxCAIL-4 rat ankle h omogenates compared with PBS-treated homogenates. Thus, increased expressio n of IL-4 via gene therapy administered in a preventative and/or therapeuti c manner reduced joint inflammation, synovial cellularity, levels of proinf lammatory cytokines, vascularization, and bony destruction in rat AIA, sugg esting that a similar treatment in humans may be beneficial.