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Arthritis Research and Therapy

, 7:R445

First Online: 17 February 2005Received: 04 November 2004Revised: 04 January 2005Accepted: 11 January 2005

Abstract

Cytokine expression was assessed during antigen-induced arthritis AIA in synovial membrane SM, inguinal lymph node LN, and spleen using competitive RT-PCR and sandwich ELISA. In the SM, early elevations of IL-1β and IL-6 mRNA by 6 hours; 450- and 200-fold, respectively correlated with the joint swelling; a 6-fold increase in tumor necrosis factor α TNFα was not significant. Not only IL-2 and IFN-γ which increased 10,000-fold and 200-fold, respectively, but also IL-5 and IL-10, increased acutely 6 hours – day 1; 3-fold and 35-fold, respectively in the SM. In general, the protein levels in the SM for IL-1β, IL-6, TNFα, IFN-γ, IL-4, and IL-10 increase from 4-fold to 15-fold matched the course of mRNA expression. In the inguinal LN, there were early mRNA elevations of IL-6 a 2.5-fold increase by 6 hours, which correlated positively with the joint swelling and IL-2 4-fold by 6 hours, as well as later rises of IL-4 and IL-5 2.5- and 4-fold, respectively, by day 3. No significant elevations of the corresponding proteins in this tissue were observed, except for IL-1β by day 6 and IL-10 by day 1. In the spleen, there were significant mRNA elevations at 6 hours of IL-1β 1.5-fold, IL-6 4-fold; positively correlated with the joint swelling, IFN-γ 3-fold, and IL-2 7- to 10-fold. IL-5 and IL-10 2- and 3-fold, respectively peaked from 6 hours to day 3 in the spleen. Increases of the corresponding proteins were significant in comparison with day 0 only in the case of IL-2 day 6. By day 6 transition to the chronic phase, the mRNA for cytokines declined to or below prearthritis levels in all the tissues studied except for IL-1β in the SM and IL-6 in the spleen. AIA is thus characterized by four phenomena: early synovial activation of macrophages, T helper Th1-like, and Th2-like cells; late, well-segregated Th2-like responses in the inguinal LN; late, overlapping Th1-like-Th2-like peaks in the spleen; and chronic elevation of synovial IL-1β mRNA and spleen IL-6 mRNA.

AbbreviationsAIAantigen-induced arthritis

ELISAenzyme-linked immunosorbent assay

IFNinterferon

ILinterleukin

LNlymph node

mBSAmethylated bovine serum albumin

PBSphosphate-buffered saline

RArheumatoid arthritis

RT-PCRreverse transcriptase polymerase chain reaction

SMsynovial membrane

ThT-helper

TNFtumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar1689 contains supplementary material, which is available to authorized users.

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