Interleukin-18 is induced in acute inflammatory demyelinating polyneuropathy

Area of Science:

• Neuroimmunology
• Cytokine Signaling
• Peripheral Nervous System Disorders

Background:

• Th1 T lymphocytes and interferon-gamma (IFN-gamma) are implicated in immune-mediated peripheral nervous system (PNS) diseases like Guillain-Barré syndrome (GBS).
• Interleukin-18 (IL-18) is a key cytokine that induces IFN-gamma production and requires caspase-1 activation for its mature form.

Purpose of the Study:

• To investigate the expression and role of IL-18 and caspase-1 in the pathogenesis of experimental autoimmune neuritis (EAN), an animal model of GBS.
• To assess IL-18 levels in serum and cerebrospinal fluid (CSF) of GBS patients compared to controls.

Main Methods:

• Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry were used to analyze IL-18 and caspase-1 mRNA and protein expression in EAN rat nerve roots.
• Enzyme-linked immunosorbent assay (ELISA) was employed to quantify IL-18 protein levels in serum and CSF samples from GBS patients and noninflammatory neurologic disease (NIND) controls.

Main Results:

• IL-18 and caspase-1 mRNA levels were upregulated in the nerve roots of EAN rats during active disease progression.
• Increased IL-18 protein expression, primarily associated with macrophages, was observed in the nerve roots of EAN rats.
• Serum IL-18 levels were significantly elevated in GBS patients compared to NIND controls.

Conclusions:

• The findings implicate the Th1-inducing cytokine IL-18 in the pathogenesis of acute immune-mediated demyelination of the PNS.
• IL-18 may serve as a potential biomarker or therapeutic target for GBS and related neuropathies.