Interferon beta treatment of multiple sclerosis increases serum interleukin-7

Background: Interleukin-7 (IL-7) is a non-redundant cytokine for T-cell development and survival. The IL-7 signaling pathway has been genetically and functionally associated with several autoimmune diseases including multiple sclerosis (MS). Objective: The objective of this paper is to elucidate the effect of the widely used immunomodulatory MS therapy interferon beta (IFN) on IL-7 homeostasis. Methods: Swedish MS patients were screened for IL-7 concentration in serum and blood cell counts. IL-7 receptor alpha chain (IL-7R) expression was determined by semi-quantitative real-time polymerase chain reaction (PCR) and flow cytometry. Results: IFN treatment led to significantly increased serum IL-7 levels (mean: 17 pg/ml) compared with healthy controls (mean: 7.6 pg/ml) and natalizumab-treated patients (mean: 5.3 pg/ml). In vitro and in vivo, peripheral blood leukocytes showed decreased IL-7R expression and IL-7 consumption upon IFN exposure, suggesting that their IL-7 responsiveness is impaired during treatment. Conclusions: MS patients undergoing IFN treatment have increased serum IL-7 levels and decreased IL-7 consumption. Given IL-7's important role in T-cell immunity, this relationship may be highly relevant for IFN's treatment efficacy.