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.
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.
Croxford
J L
JL
Neuroinflammation Group, Department of Neurochemistry, Institutes of Neurology and Ophthalmology, UCL, University of London, London, United Kingdom. jcroxfor@hgmp.mrc.ac.uk
Feldmann
M
M
Chernajovsky
Y
Y
Baker
D
D
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D016516:CD4-CD8 Ratio; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005347:Fibroblasts / Q000637:transplantation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000008:administration & dosage; D012190:Retroviridae / Q000235:genetics* / Q000276:immunology; D013116:Spinal Cord / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D013696:Temperature
D000949:Histocompatibility Antigens Class II; D009419:Nerve Tissue Proteins; C016758:spinal cord protein, Bos taurus; D016753:Interleukin-10