Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis

Clin Immunol. 2008 Sep;128(3):306-13. doi: 10.1016/j.clim.2008.04.007. Epub 2008 Jun 9.


Interferon-beta (IFN-beta) is an effective treatment for a subgroup of patients with multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN-beta is not well understood. To improve treatment considerations in MS patients predictive markers for response to IFN-beta therapy at early timepoints are needed. Here we correlated changes in serum cytokine levels (IL-13, IL-10, IL-5, IL-4, IFN-gamma) with the clinical response to IFN-beta treatment. Serum cytokine levels of 77 untreated and 43 IFN-beta treated relapsing-remitting MS patients (RRMS) were measured by ELISA, including longitudinal measurements in 17 patients. We found a significant upregulation of IL-10 and IL-5 serum cytokine levels during IFN-beta therapy. However, clinical response was only associated with IL-10 serum levels (p=0.038; positive predictive value 0.95, negative predictive value 0.43) but not with IL-5. The predictive power was increased by a combined testing of IL-10 with expression of co-signaling molecules on monocytes, that were previously shown to change during IFN-beta therapy. In a subgroup of 17 patients testing of 4 markers had a positive and negative predictive value of 1.0 for at least 2 of these markers being positive in treatment responders. The results suggest that serum IL-10 is useful to predict treatment response to IFN-beta particularly in combination with a panel of other IFN-beta dependent parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / blood
  • B7-2 Antigen / blood
  • CD40 Antigens / blood
  • Cytokines / blood*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Interferon-beta / blood
  • Interferon-beta / therapeutic use*
  • Interleukin-10 / blood*
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology*
  • Programmed Cell Death 1 Ligand 2 Protein
  • Up-Regulation


  • Antigens, CD
  • B7-2 Antigen
  • CD40 Antigens
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Interleukin-10
  • Interferon-beta