Interferon-γ facilitated adjuvant-induced arthritis at early stage.

Abstract

Interferon-γ (IFN-γ) is a versatile cytokine which broadly involves in the inflammatory diseases, mediating both immune activation and tolerance. Here, we aimed to investigate the role of IFN-γ in the initiation of adjuvant-induced arthritis (AIA). In an AIA mice model, increasing IFN-γ mRNA was observed at day 3 and peaked on day 7. At day 3, the majority of IFN-γ-producing cells were located around vessels observed by immunofluorescent staining. Recombinant IFN-γ or anti-IFN-γ antibody was injected into the AIA paw on day 2 to study the outcome of AIA. The recipients of IFN-γ showed increased synovial inflammation, whereas anti-IFN-γ antibody injection repressed the expansion of inflammatory cells. As the percentages of blood monocytes were approximately equivalent, we hypothesized that IFN-γ might impact the access of innate leucocytes from blood to expand local inflammation at this stage. Analysis of tissue CD31 and vascular cell adhesion molecule-1 (VCAM-1) expressions suggested a positive effect of these factors in the development of inflammation, and IFN-γ affected the VCAM-1 expression. To further verify this idea, mice regionally injected with IFN-γ were systematically administrated with anti-VCAM-1 antibody during AIA induction. The IFN-γ expression was inhibited, and the development of AIA was partly abolished in these mice regardless of regional IFN-γ injection. These data suggested that IFN-γ might be critical for the expansion of AIA at early stage through helping inflammatory cell access.