Contrasting responses to interferon beta-1b treatment in relapsing-remitting multiple sclerosis: does baseline interleukin-12p35 messenger RNA predict the efficacy of treatment?
Interferon (IFN)-beta treatment is effective in relapsing-remitting multiple sclerosis (RR-MS) via an as yet unidentified mechanism. In the present study, we investigated whether the expression of messenger RNA (mRNA) encoding the interleukin (IL)-12 subunits p40 and p35, IL-12 receptor chains, IL-18, tumor necrosis factor-alpha (TNFalpha), IFNgamma, IL-10, IL-4, or transforming growth factor-beta in unstimulated whole blood of 26 RR-MS patients changed during 6 months of IFNbeta-1b treatment. In these patients, a significant change was found in TNFalpha mRNA, whereas changes in IL-12 receptor-beta2 and IL-10 mRNA showed a trend. IFNbeta-1b-related changes in cytokine mRNA expression were next evaluated in clinical subgroups of RR-MS patients classified as either clinical responders or nonresponders on the basis of Expanded Disability Status Scale progression and the number of relapses and steroid interventions needed in the 2 years before initiation of treatment compared with the 2 years after initiation of treatment. These subgroups showed different response patterns to IFNbeta-1b treatment with respect to IL-10, TNFalpha, and IL-18 only. Surprisingly, clinical responders displayed no change in these cytokines, whereas nonresponders showed a decrease in TNFalpha and IL-18 mRNA as well as a transient increase in IL-10 mRNA. Baseline levels of IL-12p35 mRNA were lower in the responders compared with the nonresponders: this marker correctly predicted the clinical outcome in 81% of the 26 patients under investigation.
van Boxel-Dezaire
A H
AH
Division of Immunological and Infectious Diseases, TNO Prevention of Health, Leiden University Medical Center, The Netherlands.
van Trigt-Hoff
S C
SC
Killestein
J
J
Schrijver
H M
HM
van Houwelingen
J C
JC
Polman
C H
CH
Nagelkerken
L
L
D000328:Adult; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000235:genetics*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000235:genetics*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics*; D013997:Time Factors
D012333:RNA, Messenger; D000068576:Interferon beta-1b; D018664:Interleukin-12; D016899:Interferon-beta; D000068556:Interferon beta-1a