Protective Mechanisms by ω-6 Lipids in Experimental Autoimmune Encephalomyelitis (EAE) are Associated with Cytokines and Eicosanoids

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune and demyelinating disease of the central nervous system (CNS) inducible in susceptible rodents and other mammalian species by active or adoptive sensitization to CNS constituents [I]. EAE can be induced by inoculation with neuroantigens such as myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG) and their peptides [ 1-31. We have reported previously that oral administration of lipid, rich in the omega-6 fatty acid ylinolenic acid, can completely protect Lewis rats from spinal cord homogenate induced EAE [4]. In contrast we have found that omega-3 fatty acids exacerbate and prolong EAE in Lewis rats [5,6]. The mechanisms by which y-linolenic acid modifies the immune response in EAE is unclear. We have, therefore, investigated the effects of oral feeding a y-linolenic acid-rich plant lipid (Borago offcinalis) on MOG-peptide (aa 92-106) induced EAE in SJL mice. Lymphocyte proliferative responses and the production of cytokines and eicosanoids ex vivo were also investigated.MOG-peptide (aa 92-106) induced EAE, in SJL mice, was carried out as described previously [3]. Mice were galvaged daily with 250-300 1. 11 plant lipid (B. oficinalis) from day 7 after EAE induction and sacrificed at day 21. Mice were examined daily and clinical signs assessed. Brain and spinal cord were processed for routine histology [3]. Mononuclear cells were isolated from spleens by density centrifugation and cultured for 72 hr with ConA (lpg/ml), PPD (1:lO) and MOG peptide (aa 92-106

Role of Fatty Acids in the Resolution of Autoimmune and Inflammatory Diseases

“…Harbige et al also demonstrated that gamma linoleic acid (GLA) supplementation could reduce the severity of both acute EAE and the relapsing phases of chronic. Further analysis revealed an increase in production of transforming growth factor -1 and PGE 2 , both associated with a reduction in the inflammatory response in EAE models (Harbige et al, 1995;Harbige et al, 1997;Harbige et al, 2000).…”