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.
Croxford JL., Feldmann M., Chernajovsky Y., Baker D.
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.