Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis.
Multiple sclerosis (MS) is supposedly a T-cell mediated autoimmune disorder of the central nervous system. Cytokines and other molecules involved in the regulation of apoptosis are thought to be of importance for the pathogenesis of MS. In this study, the mRNA levels of interleukin 18 (IL-18), IL-1beta and their processing enzyme caspase-1 were quantified by a competitive RT-PCR method in unstimulated peripheral blood mononuclear cells (PBMCs) in MS patients never treated with disease modifying drugs. Western blot was used to support the expression pattern at the protein level. We found that the expression of caspase-1 and IL-18 was significantly increased in MS patients compared with healthy controls. Analysis of clinical subgroups revealed that caspase-1 was increased in all subgroups, whereas IL-18 was upregulated in chronic progression (P=0.001) and relapsing MS patients in remission (P=0.002) but not significantly during relapses (P=0.12). mRNA levels of IL-1beta were not significantly altered in MS except for a possible decrease in chronic progression (P=0.03). An increased IL-18 expression, potentially augmented at the mature protein level, may indicate a pathway worth considering in future therapeutic strategies in MS.
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
Wen-Xin
WX
Huang
Ping
P
Huang
Jan
J
Hillert
D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D020170:Caspase 1 / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D020382:Interleukin-18 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D020382:Interleukin-18; D012333:RNA, Messenger; D020170:Caspase 1