Interleukin-11 regulates autoimmune demyelination

• Published in: Journal of interferon & cytokine research Vol. 30; no. 1; p. 52
• Main Author: Gurfein, Blake T
• Format: Journal Article
• Language: English
• Published: Mary Ann Liebert, Inc 01.01.2010
• Subjects: Care and treatment; Cellular signal transduction; Health aspects; Interleukin-11; Multiple sclerosis; Risk factors; United States
• ISSN: 1079-9907; 1557-7465
• DOI: 10.1089/jir.2010.3001.diss

Multiple Sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Selective destruction of myelin is the foremost pathological hallmark of the early stages of MS disease progression. Later in the disease course progressive axonal transection is also observed and is associated with permanent neurologic disability. Current therapies for MS target inflammation but do not directly address neuroprotection or lesion repair. Cytokines of the gp130 family regulate the survival and differentiation of both neural and immune cells, and we recently identified expression of the family member interleukin-11 (IL-11) in active MS plaques. Here, we show that IL-11 regulates the clinical course and neuropathology of experimental autoimmune encephalomyelitis (EAE), a demyelinating model that mimics many of the clinical and pathologic features of MS. Importantly, the effects of IL-11 are achieved via a combination of immunoregulation and direct neuroprotection. IL-11 receptor-alpha null (IL-11Ra super(-/-)) mice displayed a significant increase in clinical severity and neuropathology of EAE compared with wild-type littermates. Inflammation, demyelination, and oligodendrocyte loss were all exacerbated in IL-11Ra super(-/-) animals. Conversely, wild-type mice treated with IL-11 displayed milder clinical signs and neuropathology than vehicle-treated controls. In cocultures of murine MOG 35-55-specific CD4+ T lymphocytes and CD11c+ antigen-presenting cells (APCs), IL-11 treatment resulted in a significant decrease in T cell-derived effector cytokine production. This unexpected effect was generated by modulation of CD11c+ APC-mediated lymphocyte activation, and was associated with a decrease in the size of the CD11c+ cell population. Conversely, IL-11 strongly reduced apoptosis and potentiated mitosis in primary cultures of mouse oligodendrocyte progenitors (OPCs). Collectively, these data reveal that IL-11 regulates inflammatory demyelination via a unique combination of immunoregulation and neuroprotection. IL-11 signaling may represent a therapeutic avenue to restrict CNS inflammation and potentiate oligodendrocyte survival in autoimmune demyelinating disease.