Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain.

• DOI: 10.1084/jem.176.5.1355
• Publication Date: 2004-06-24T07:56:10Z
• Authors: S J Khoury; W W Hancock; H L Weiner
• Keywords: Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) in the Lewis rat is a self-limited inflammatory process localized to central nervous system that induced by injection of myelin basic protein (MBP) adjuvant. Oral administration MBP suppresses EAE, and this suppression mediated CD8+ T cells adoptively transfer protection suppress both vitro vivo release transforming growth factor (TGF) beta after antigen-specific triggering. Furthermore, oral tolerance enhanced concomitant lipopolysaccharide (LPS). The present study was undertaken determine whether disease course EAE its tolerization associated with distinct patterns cytokine expression target organ. Detailed immunohistology brain performed at peak clinical (day 14 immunization) recovery 18) control (ovalbumin [OVA]-fed), MBP-fed, plus LPS-fed animals. Brains from OVA-fed animals showed perivascular infiltration activated mononuclear which secreted cytokines interleukins (IL) 1, 2, 6, 8, TNF-alpha, interferon gamma. inhibitory TGF-beta IL-4, prostaglandin E2 (PGE2) were absent. In orally tolerized there marked reduction infiltrate downregulation all cytokines. addition, upregulation TGF-beta. LPS animals, addition cytokines, IL-4 PGE2, presumably secondary activation an additional population immunoregulatory cells. had recovered 18), staining for diminished, appearance IL-4. These results suggest either or occurs during natural related secretion factors actively