Different therapeutic outcomes in experimental allergic encephalomyelitis dependent upon the mode of delivery of IL-10: a comparison of the effects of protein, adenoviral or retroviral IL-10 delivery into the central nervous system.

Journal article

Experimental allergic encephalomyelitis (EAE) is a CNS autoimmune disease mediated by the action of CD4(+) T cells, macrophages, and proinflammatory cytokines. IL-10 is a cytokine shown to have many anti-inflammatory properties. Studies have shown both inhibition and exacerbation of EAE after systemic IL-10 protein administration. We have compared the inhibitory effect in EAE of Il10 gene delivery in the CNS. Fibroblasts transduced with retroviral vectors expressing IL-10 could inhibit EAE. This was not associated with a prevention of cellular recruitment but an alteration in their phenotype, notably an increase in the numbers of CD8(+) T and B cells. In marked contrast, CNS delivery of adenovirus coding for mouse IL-10 or IL-10 protein performed over a wide dose range failed to inhibit disease, despite producing similar or greater amounts of IL-10 protein. Thus the action of IL-10 may differ depending on the local cytokine microenvironment produced by the gene-secreting cell types.

Authors: Croxford, J; Feldmann, M; Chernajovsky, Y; Baker, D

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 166
• Issue: 6
• Pages: 4124-4130
• Publication date: 2001-03-01
• DOI: 10.4049/jimmunol.166.6.4124
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Nerve Tissue Proteins; Interleukin-10; Down-Regulation; Cell Line, Transformed; Animals; Temperature; Mice, Inbred Strains; Fibroblasts; Mice; Adenoviridae; Encephalomyelitis, Autoimmune, Experimental; Histocompatibility Antigens Class II; Injections, Subcutaneous; Gene Therapy; Spinal Cord; Cell Movement; Injections, Intraventricular; Genetic Vectors; Retroviridae; CD4-CD8 Ratio