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Horm Metab Res 2002; 34(10): 561-569
DOI: 10.1055/s-2002-35417
Original Basic
© Georg Thieme Verlag Stuttgart · New York

A Murine Interleukin-4-Ig Fusion Protein Regulates the Expression of Th1- and Th2-Specific Cytokines in the Pancreas of NOD Mice

M.  Walz 1 , L.  Overbergh 2 , C.  Mathieu 2 , H.  Kolb 1 , S.  Martin 1
  • 1German Diabetes Research Institute, Clinical Department, Heinrich-Heine-University, Duesseldorf, Germany
  • 2Katholieke Universiteit Leuven, LEGENDO, Gasthuisberg, Leuven, Belgium
Further Information

Publication History

Received: 11 April 2002

Accepted after revision: 3 July 2002

Publication Date:
19 November 2002 (online)

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Abstract

Interleukin (IL)-4 is a key cytokine in T-helper type 2 (Th2) immune response. We have constructed a dimeric IL-4 molecule consisting of the murine IL-4 and the murine Fc part of IgG2a. We first tested the biological activity of the chimeric protein by in vitro studies using isolated murine spleen cells. IL-4-Ig was found to downregulate LPS-induced IFN-γ and TNF-α production. The immunomodulatory potential of the fusion protein was also analyzed in non-obese diabetic (NOD) mice, an animal model for human type 1 diabetes. Female NOD mice aged 10 weeks were treated once with cyclophosphamide to accelerate and synchronize the progression of insulitis. Treatment with IL-4-Ig induced strong modulation of the pancreatic cytokine balance. Expression was downregulated for both Th1-specific cytokine IFN-γ and the Th2-specific cytokine IL-10. IL-12p40 expression was only slightly affected. Interestingly, infiltration increased in the islets of IL-4-Ig-treated animals, and therefore did not correlate with the decreased IFN-γ expression. Hence, IL-4-Ig did not prevent the progression from peri- to intra-insulitis, but suppressed inflammatory cytokine production. In most experiments, the biological activity of IL-4-Ig and IL-4 was comparable. We conclude that treatment with the chimeric protein IL-4-Ig effectively downregulates Th1 responses but simultaneously augments intra-islet infiltration.

Key words

NOD Mice - Cyclophosphamide - IL-4-Ig - Fusion Proteins - Th1/Th2 Cytokines

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Dr. M. Walz

Department of Dermatology, Heinrich-Heine-University

Moorenstrasse 5 · 40225 Duesseldorf · Germany ·

Phone: + 49 (211) 81 18 342

Email: markus.walz@med.uni-duesseldorf.de

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