Subcutaneous interferon-beta injections in patients with multiple sclerosis initiate inflammatory skin reactions by local chemokine induction

J Neuroimmunol. 2005 Nov;168(1-2):175-82. doi: 10.1016/j.jneuroim.2005.07.011. Epub 2005 Aug 26.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Biopsy
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay / methods
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Injections, Subcutaneous / methods
  • Interferon-beta / therapeutic use*
  • Male
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Skin / drug effects*
  • Skin / pathology

Substances

  • Antigens, CD
  • Chemokines
  • Cytokines
  • Interferon-beta