Intra-articular IL-4 gene therapy in arthritis: anti-inflammatory effect and enhanced Th2activity

Collagen II-pulsed antigen-presenting cells genetically modified to secrete IL-4 down-regulate collagen-induced arthritis

“…of either viral vectors expressing IL-4 22,23,33 or naked DNA plasmids into arthritic mice (our unpublished observations). Thus, it is plausible that higher amounts of regulatory cytokines are required to block the ongoing flare up of CIA than to control the initiation of immune response.…”

“…21 In the current study, we hypothesized that the antigenprocessing capacity and migratory properties of various APC may represent an appropriate endogenous system for site-specific delivery of therapeutic transgene proteins during autoimmune diseases. Since we and others have previously reported that gene therapy with the Th2 cytokine IL-4 inhibits animal models of rheumatoid arthritis including CIA, 7,[22][23][24][25] we explored the ability of APC transduced with murine IL-4 gene and pulsed with CII to interfere with the pathological process developing in murine CIA. Our hypothesis was tested by using two types of APC engineered to secrete this cytokine: B cells which were reported to elicit preferentially a Th2 response 26 and macrophages that can migrate to inflamed tissues and that we found to be the most potent APC in the response towards CII.…”

An inflammation-inducible adenoviral expression system for local treatment of the arthritic joint

“…The 'contralateral effect', that is the administration of the expression vector in one joint to suppress arthritis in distal or contralateral joints, has been reported by many laboratories. [47][48][49][50][51][52] This study, which shows activation of the IL-1/IL-6 enhancer-promoter in the contralateral joints by signals derived from the arthritic joint, suggests that there is crosstalk between joints. Treatment of one joint may interfere with this crosstalk and by this suppresses arthritis in the other contralateral joint.…”

Vectors for the treatment of autoimmune disease

“…in an experimental arthritis model. 76 Greatest success with retroviral vector gene therapy of experimental animal models of autoimmune diseases has been achieved following ex vivo transduction of various cell types. For example, bone marrow-derived dendritic cells (DCs) were transduced with the IL-4 gene and proved effective in inhibiting murine CIA.…”