Interleukin-18 is induced in acute inflammatory demyelinating polyneuropathy.
T lymphocytes of the Th1 subset producing the proinflammatory cytokine interferon-gamma (IFN-gamma) have been implicated in the pathogenesis of immune-mediated diseases of the peripheral nervous system (PNS) such as the acute Guillain-Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN). Interleukin-18 (IL-18) is a potent IFN-gamma-inducing cytokine that is synthesized as an inactive precursor molecule and cleaved by caspase-1 into its mature active form. In our present study we analyzed the expression of IL-18 and caspase-1 in the nerve roots of EAN rats using reverse transcriptase-polymerase chain reaction and immunocytochemistry. Using an enzyme-linked immunosorbent assay, we furthermore determined IL-18 protein levels in paired serum and cerebrospinal fluid (CSF) samples from patients with GBS as well as from noninflammatory neurologic disease (NIND) controls. In EAN, IL-18 and caspase-1 mRNA levels in the nerve roots increased during the stage of active disease progression. Immunocytochemically, both perivascular and parenchymal IL-18 protein expression was increased in the roots of EAN rats and mainly associated with ED1+ macrophages stained on serial sections. IL-18 serum levels were significantly higher in GBS patients than in NIND controls (238+/-71 vs. 42+/-7 pg/ml, P<0.001). Our data implicate the Th1-inducing cytokine IL-18 in the pathogenesis of acute immune-mediated PNS demyelination.
Jander
S
S
Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany. jander@uni-duesseldorf.de
Stoll
G
G
D000818:Animals; D020170:Caspase 1 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013126:Spinal Nerve Roots / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology*
D020382:Interleukin-18; D012333:RNA, Messenger; D007371:Interferon-gamma; D020170:Caspase 1