In situ cytokine immune responses in acute disseminated encephalomyelitis: insights into pathophysiologic mechanisms.
Acute disseminated encephalomyelitis (ADEM) is thought to be an autoimmune disorder of the central nervous system in which myelin is targeted. Pathological studies on closely related human diseases (eg, multiple sclerosis) and on animal models for these demyelinating disorders have suggested the involvement of cytokines. Studies on peripheral immunocytes and on cerebrospinal fluid revealed the presence of cytokine-mediated responses in ADEM. We carried out this neuroimmunopathologic exploration and report for the first time the in situ expression of "inflammatory" cytokines in ADEM. Moreover, we note a particular spatial and molecular pattern whereby tumor necrosis factor-alpha and interleukin (IL)-1beta are intensely expressed, whereas IL-6 is absent. Differential expression at different levels of the neuraxis was also noticed. Our findings suggest that these cytokines, reported to be toxic to myelin, are implicated in the molecular cascade, resulting in the neural damage. These observations might provide insights into molecular pathways involved in the immunopathogenesis of ADEM and might open new horizons in neuroimmunomodulation and anticytokine treatment.
Kadhim
Hazim
H
Unité de Neuropathologie, Service d'Anatomopathologie, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
De Prez
Carine
C
Gazagnes
Marie-Dominique
MD
Sébire
Guillaume
G
D000368:Aged; D001921:Brain / Q000473:pathology; D016207:Cytokines / Q000032:analysis*; D004673:Encephalomyelitis, Acute Disseminated / Q000175:diagnosis / Q000276:immunology*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018836:Inflammation Mediators; D007375:Interleukin-1 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008279:Magnetic Resonance Imaging; D013116:Spinal Cord / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha