Subcutaneous interferon-beta injections in patients with multiple sclerosis initiate inflammatory skin reactions by local chemokine induction.
Subcutaneous Interferon-beta (IFN-beta) injections for the treatment of multiple sclerosis (MS) frequently cause inflammatory injection site reactions. To study the role of chemokines we obtained skin biopsies from 7 MS patients 24 h after injection. At the IFN-beta but not at the contralateral placebo injection sites, we observed strong IP-10/CXCL10 and moderate MCP-1/CCL2 expression associated with extensive perivascular, highly CXCR3-positive T cell and macrophage infiltrates. Primary human skin cells displayed a comparable pattern of chemokine induction after stimulation with IFN-beta in vitro. IFN-beta may therefore trigger inflammatory skin reactions through local chemokine induction followed by rapid immune cell extravasation.
Buttmann
Mathias
M
Department of Neurology, Julius-Maximilians-University, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. m.buttmann@mail.uni-wuerzburg.de
Goebeler
Matthias
M
Toksoy
Atiye
A
Schmid
Sybille
S
Graf
Wolfgang
W
Berberich-Siebelt
Friederike
F
Rieckmann
Peter
P
D015703:Antigens, CD / Q000378:metabolism; D001706:Biopsy; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007279:Injections, Subcutaneous / Q000379:methods; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000187:drug effects* / Q000473:pathology
D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D016899:Interferon-beta