Gene Therapy for Autoimmune Diseases

Autoimmune disease is a pathogenic condition in which one's immune system mistakenly targets and attacks person's own cells, tissues, and organs. Inflammation is a prevalent symptom for this disease caused by the excessive presence of large number of immune cells and molecules in the target site of the body. Against autoimmune diseases or other inflammatory conditions, the delivery of cytokines or cytokine inhibitors through gene therapy is proved very effective. Interferon y (IFN-y), in-terleukin-1 (IL-1, a or ]3), IL-12, and tumor necrosis factor a (TNFa) are the most frequently addressed inflammatory cytokines in illness related to autoimmune/inflammatory diseases. Other than these cytokines, transforming growth factor j3 (TGF (3) is also a key regulatory cytokine (53), because TGF )3 inhibits T- and B-cell responses, dysregulation of which lead to elevation of autoimmune disease conditions.

In animal models, pDNA constructs with the encoding anti-inflammatory cytokine genes for IL-10 (54), IL-4 (55), and TGF j31 (56) were injected into either tibialis anterior or rectus femoris muscles in nonobese diabetic (NOD) mouse against autoimmune diabetic disease. Although there was no marked decrease in severity of insulitis, the diabetes was reduced in NOD mice injected with IL10 compared with nontreated NOD mice. In another experiment, treatment of autoimmunity prone NOD mice with pCMV-TGF-j31 (57) resulted in considerable elevation of TGF-p 1 level in the plasma. The increased levels of exerted various immunosuppressive effects such as there was suppression of de-layed-type hypersensitivity (DTH) and prevention of insulitic and diabetic incidence in this kind of mice. TGF-/31, IL-4, and IFN-y gene coding plasmid vectors were also injected IM to rodent models for treatingexperimental allergic encephalomyelitis (EAE) (57), systemic lupus erythematosus (SLE) (58), colitis (59), and streptococcal cell wall-induced arthritis (SCW-arthritis) (60).

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Arthritis Relief and Prevention

Arthritis Relief and Prevention

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