METHYLPREDNISOLONE PREVENTS REJECTION OF INTRASTRIATAL GRAFTS OF XENOGENEIC EMBRYONIC NEURAL TISSUE IN ADULT-RATS

We studied the effects of high-dose methylprednisolone on the survival of intrastriatal neural xenografts and the host responses against the m. Dissociated mesencephalic tissue from inbred mouse (CBA-strain) emb ryos was transplanted to the intact striatum of adult Sprague-Dawley r ats. The rats received either daily injections of methylprednisolone ( 30 mg/kg), or cyclosporin A (10 mg/kg), or no immunosuppressive treatm ent. Two or six weeks after transplantation, there was good survival o f xenografts in both the methylprednisolone- and cyclosporin A-treated rats. In contrast, the xenografts in untreated control rats were all rejected by six weeks. There was no marked difference in the degree of expression of MHC class I and II antigens and the accumulation of act ivated astrocytes and microglial cells/macrophages between the three g roups. However, both methylprednisolone and cyclosporin A reduced infi ltration of T lymphocytes to the transplantation sites. The expression of pro-inflammatory cytokines (interferon-gamma, tumour necrosis fact or-alpha, interleukin-6) in and around the grafts was lower in the met hylprednisolone- and cyclosporin A-treated groups than in untreated co ntrol rats. Although high-dose methylprednisolone caused significant b ody weight loss, we conclude that this treatment can prevent rejection of intrastriatal grafts of xenogeneic embryonic neural tissue in the adult.