Cytokine expression and synovial pathology in the initiation and spontaneous resolution phases of adjuvant arthritis: Interleukin-17 expression is upregulated in early disease

The aim of this study was to understand the immune processes controlling th e initiation and spontaneous resolution of adjuvant arthritis (AA). We inve stigated synovial T-cell recruitment and mRNA expression of IL-17 and other important disease related cytokines, IFN-gamma, IL-2, IL-4, TNF and TGF-be ta in inguinal lymph node (ILN) and synovial membrane (SM). Arthritis sever ity was assessed by a numerical rating score and rats were sacrificed every 3-4 days postadjuvant induction. Further assessment involved quantitative radiology and histology of the ankle joints on each day, and the ILN and SM were removed for RNA extraction. Cytokine mRNA expression was measured usi ng RT-PCR and densitometry. Paraffin sections of rat ankle joints were stai ned for T-cells (CD3) by immunohistochemistry. In the ILN, there was an inc rease in IL-17, TNF and IFN-gamma expression in the early stages of disease , with a secondary sustained increase in IFN-gamma expression. In the SM, t here was expression of T-cell cytokines in early arthritis (day 13), and pr olonged TNF and TGF-beta expression, which reflected disease progression. I L-4 mRNA expression increased in the later stages of AA. Synovial T-cell nu mbers transiently increased at day 6, and remained high from days 13-28. In creased pro-inflammatory cytokine expression, including IL-17, in the ILN r eflects the initiating events in the early stage of disease. IL-17 may ther efore play an important role in the pathogenesis of AA. The increase in IL- 4 (an anti-inflammatory cytokine) in the SM in the later stages of AA sugge sts that IL-4 is involved in the spontaneous resolution of AA. The initial increase in IFN-gamma in the ILN may reflect a pro-inflammatory response, w hile the prolonged secondary increase may indicate activation of regulatory T-cells.