Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

Michael R. Pranzatelli, Front Immunol. 2018; 9: 557. Published online 2018 Apr 4. doi:10.3389/fimmu.2018.00557

The concept and recognized components of “neuroinflammation” are expanding at the intersection of neurobiology and immunobiology. Chemokines (CKs), no longer merely necessary for immune cell trafficking and positioning, have multiple physiologic, developmental, and modulatory functionalities in the central nervous system (CNS) through neuron–glia interactions and other mechanisms affecting neurotransmission. They issue the “help me” cry of neurons and astrocytes in response to CNS injury, engaging invading lymphoid cells (T cells and B cells) and myeloid cells (dendritic cells, monocytes, and neutrophils) (adaptive immunity), as well as microglia and macrophages (innate immunity), in a cascade of events, some beneficial (reparative), others destructive (excitotoxic).
Filling in knowledge gaps between pediatric- and adult-onset neuroinflammation by systematic collection of CSF data on CKs/cytokines in temporal and clinical contexts and incorporating immunobiomarkers in clinical trials is a challenge hereby set forth for clinicians and researchers.
Interferon-gamma, the sole type 2 IFN, binds to the IFN-γ-R1 and IFN-γ-R2 receptors (also denoted IFNGR1 and R2). IFN-γ-1b is FDA-approved for chronic granulomatous diseases and osteopetrosis. A phase III study (NCT024155127) of IFN-γ-1b for the treatment of Friedreich ataxia has been completed recently, but without study results yet, based on positive results from as phase II study. Treatment with IFN-γ exacerbated MS.
In preclinical studies, administration of G-CSF in a murine model of Friedreich ataxia resulted in clinical improvement and reduction in inflammation and gliosis. IL-10 is such a powerful counteractant of pro-inflammatory cytokines, one would hope there is more progress in this area.

 Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines