Open Access Research article

Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators?

Joseph Paquet1, Jean-Christophe Goebel1, Camille Delaunay2, Astrid Pinzano1, Laurent Grossin1, Christel Cournil-Henrionnet1, Pierre Gillet1, Patrick Netter1, Jean-Yves Jouzeau1 and David Moulin1*

Author Affiliations

1 Physiopathologie, Pharmacologie et Ingénierie Articulaire - PPIA-UMR 7561 CNRS UHP, Université de Lorraine, Faculté de Médecine, BP 184, 54505 Vandoeuvre Les Nancy, France

2 Anatomie et Cytologie Pathologiques - CHU Nancy Brabois, 54505 Vandoeuvre Les Nancy, France

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Arthritis Research & Therapy 2012, 14:R60  doi:10.1186/ar3774

Published: 13 March 2012

Abstract

Introduction

We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis.

Methods

We performed a follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and confronted their protein level changes with molecular, biochemical, histological and clinical events occurring in the course of the disease.

Results

The time-scheduled findings in arthritic joints correlated with time-dependent changes of cytokine amounts in joint effusions but not with their blood levels. From seven hours after sensitization, high levels of chemokines (MCP-1, MIP1α, GRO/KC, RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas perivascular infiltration occurred in the synovium; local release of inflammatory cytokines (IFNγ, IL-1β, IL-6) preceded the spreading of inflammation and resulted in progressive degradation of cartilage and bone. Finally a local overexpression of several cytokines/adipocytokines poorly described in arthritis (IL-13, IL-18, leptin) was observed.

Conclusions

Distinct panels of cytokines were found in arthritic fluid during AIA, and the expected effect of mediators correlated well with changes occurring in joint tissues. Moreover, multiplex analysis could be helpful to identify new pathogenic mediators and to elucidate the mechanisms supporting the efficacy of putative targeted therapies.