Potential for interferon beta-induced serum antibodies in multiple sclerosis to inhibit endogenous interferon-regulated chemokine/cytokine responses within the central nervous system.
BACKGROUND
A proportion of patients with multiple sclerosis (MS) receiving systemic interferon beta therapy will develop serum neutralizing antibodies (NAbs) that can reduce the activity of the drug. Interferon-beta (IFN-beta) is produced by glial cells within the central nervous system. Although systemic interferon beta does not access the central nervous system, titers of serum NAbs may be sufficient that some will access the central nervous system.


OBJECTIVE
To address whether serum samples that contain high titers of NAbs could inhibit glial cell production of chemokines and cytokines that are regulated by endogenous IFN-beta.


METHODS
We used an in vitro assay involving toll-like receptor 3 ligand (polyinosinic-polycytidylic acid) signaling to assess the effect of serum samples containing high titers of NAbs (1800-20 000 U) on production of the chemokine CXCL10 and the cytokine interleukin 6 by human astrocytes.


RESULTS
Serum samples positive for NAbs significantly inhibited polyinosinic-polycytidylic acid-induced CXCL10 and IL-6 production by astrocytes.


CONCLUSIONS
High-titer NAbs to interferon beta may block endogenous IFN-beta function and alter the chemokine/cytokine microenvironment within the central nervous system, thereby modulating the profile and course of the local inflammatory response.
Shapiro
Aaron M
AM
Neuroimmunology Unit and Multiple Sclerosis Clinic, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec.
Jack
Carolyn S
CS
Lapierre
Yves
Y
Arbour
Nathalie
N
Bar-Or
Amit
A
Antel
Jack P
JP
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D006801:Humans; D016899:Interferon-beta / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D044967:Serum / Q000502:physiology
D000906:Antibodies; D016207:Cytokines; D016899:Interferon-beta