Different therapeutic outcomes in experimental allergic encephalomyelitis dependant 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 CD(4+) 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 CD(8+) 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.