The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-beta 1) up-regulation and increased prostaglandin E-2 (PGE(2)) production

Polyunsaturated fatty acids are known to affect the immune response and adm inistration of the omega-6 fatty acid linoleic acid has been reported to be beneficial in multiple sclerosis (MS) and EAE. In this study we have inves tigated the effects of oral feeding of plant lipid rich in the omega-6 fatt y acid gamma-linolenic acid from Borago officinalis on acute and relapse di sease and the immune response in EAE using SJL mice. EAE was induced by an encephalitogenic peptide (92-106) of myelin oligodendrocyte glycoprotein (M OG), and mice were fed the plant lipid daily from 7 days after EAE inductio n to assess the effects on acute disease and from day 25 to assess the effe cts on disease relapse. The clinical incidence and histological manifestati ons of acute EAE, and the clinical relapse phase of chronic relapsing EAE ( CREAE) were markedly inhibited by omega-6 fatty acid feeding. A significant increase in the production of TGF-beta1 in response to concanavalin A (Con A) at day 13 and a significant increase in TGF-beta1 and PGE(2) to Con A, PPD and MOG peptide (92-106) at day 21 were detected in spleen mononuclear cells from fatty acid-fed mice. There was no difference in interferon-gamma , IL-4 and IL-2 production between the fatty acid-fed and control groups. S ignificantly higher TGF-beta mRNA expression was found in the spleens of om ega-6 fatty acid-fed mice at day 21. There were no differences in spleen ce ll proliferative response to Con A, PPD and MOG peptide (92-106). Biochemic al analysis of spleen cell membrane fatty acids revealed significant increa ses in the eicosanoid precursor fatty acids dihomo-gamma -linolenic acid an d arachidonic acid in response to gamma-linolenic acid feeding, indicating rapid metabolism to longer chain omega-6 fatty acids. These results show th at oral feeding of gamma-linolenic acid-rich plant lipid markedly affects t he disease course of acute EAE and CREAE and is associated with an increase in cell membrane long chain omega-6 fatty acids, production of PGE(2) and gene transcription and, on activation, secretion of TGF-beta1.