Cytokine and IL-12 receptor mRNA discriminate between different clinical subtypes in multiple sclerosis.
Little is known about the involvement of cytokines in the pathogenesis of primary progressive (PP) multiple sclerosis (MS). We evaluated in this cross-sectional study whether IL-18, IL-12p35, IL-12p40, TNF-alpha, IFN-gamma, IL-10, IL-4, TGF-beta, IL-12Rbeta1, and IL-12Rbeta2 mRNA expression in unstimulated white blood cells showed significant differences between relapsing-remitting (RR), secondary progressive (SP) and PP MS patients, and healthy controls. All clinical subtypes showed unique mRNA expression patterns as compared to the controls. Both RR and SP patients displayed increased levels of IL-12p40, IL-18, and TGF-beta mRNA compared to controls, whereas PP patients showed only increased IL-18 mRNA levels. Both in PP and SP patients, IFN-gamma and IL-10 mRNA were decreased compared to RR patients and controls. PP patients were unique in that they showed decreased IL-12Rbeta1 mRNA. In conclusion, our data show that the assessment of cytokine (receptor) mRNA profiles is useful to discriminate between the different clinical subtypes and suggest that different cytokines are involved in the pathogenesis of PP MS as compared to RR and SP MS.
van Boxel-Dezaire
A H
AH
TNO Prevention and Health, Division of Immunological and Infectious Diseases, PO Box 2215, 2301 CE Leiden, The Netherlands.
Smits
M
M
van Trigt-Hoff
S C
SC
Killestein
J
J
van Houwelingen
J C
JC
Polman
C H
CH
Nagelkerken
L
L
D000328:Adult; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12; D016212:Transforming Growth Factor beta / Q000235:genetics
D016207:Cytokines; D020382:Interleukin-18; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12