Open Access Research article

The severity of experimental arthritis is independent of IL-36 receptor signaling

Céline Lamacchia12, Gaby Palmer12, Emiliana Rodriguez12, Praxedis Martin12, Solenne Vigne12, Christian A Seemayer3, Dominique Talabot-Ayer12, Jennifer E Towne4 and Cem Gabay12*

Author Affiliations

1 Division of Rheumatology, Department of Internal Medicine, University Hospital of Geneva, 26 avenue Beau-Séjour, 1211 Geneva 14, Switzerland

2 Department of Pathology-Immunology, University of Geneva School of Medicine, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland

3 Novartis Pharma AG, Translational Medicine, NIBR, WSJ386.10.48, PO Box, 4002 Basel, Switzerland

4 Department of Inflammation Research, Amgen Inc., 1201 Amgen Court West, Seattle, WA 98119, USA

For all author emails, please log on.

Arthritis Research & Therapy 2013, 15:R38  doi:10.1186/ar4192

Published: 1 March 2013

Abstract

Introduction

Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis.

Methods

Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring.

Results

IL-36R, IL-36Ra and IL-36γ mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice.

Conclusions

The development and severity of experimental arthritis are independent of IL-36R signaling.