Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF.
To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.
Mei
Feng-Jun
FJ
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Ishizu
Takaaki
T
Murai
Hiroyuki
H
Osoegawa
Manabu
M
Minohara
Motozumi
M
Zhang
Kun-Nan
KN
Kira
Jun-ichi
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018925:Chemokines / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000134:cerebrospinal fluid; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007118:Immunoassay / Q000379:methods; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000134:cerebrospinal fluid* / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D020293:Vasculitis, Central Nervous System / Q000134:cerebrospinal fluid* / Q000473:pathology
D018925:Chemokines; D016207:Cytokines