Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation

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Science Translational Medicine  28 Feb 2018:
Vol. 10, Issue 430, eaao2304
DOI: 10.1126/scitranslmed.aao2304

IL-4 empowers axons

Multiple sclerosis (MS) is a neuroinflammatory disorder, and current therapies focus on altering immune activity to reduce symptoms. Vogelaar and colleagues tested the ability of intrathecally applied IL-4, a cytokine typically associated with T helper type 2 responses, to treat established disease in several experimental autoimmune encephalomyelitis (EAE) models. IL-4 treatment led to reduced clinical scores, improved locomotor activity, and diminished axon damage. Somewhat surprisingly, the beneficial effects of IL-4 did not depend on T cell modulation in the chronic disease phase. The receptor for IL-4 was observed in postmortem brain histology of several MS patients, and they demonstrated that IL-4 could act directly on neurons in vitro. They also showed benefits of intranasal IL-4 administration in one of the EAE models, which could be a promising avenue to pursue in the clinic.

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