Displayed any significant change in mRNA level in the synovium of
Displayed any significant change in mRNA level in the synovium of the saline-injected (contralateral) knee.Overall pattern of mediator levels in biological fluidswere observed in the joint fluid from saline-injected knees or in sera. IL-2 and IL-9 contents increased less rapidly than IL-17 and IFNg in the arthritic knee (2- to 2.5-fold induction by D1) and showed a secondary but non-significant increase by D7 (Figure 4b,d).Cytokines with a sustained or a late release in arthritic fluidAs shown in Figure 2, the global analysis of arthritisinduced changes in cytokine amounts were more marked in SF than in the bloodstream, regardless PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27872238 of the functional class considered. Mediators displayed two main profiles of variation in arthritic joints, and cytokines showed either an early and transient increase or a delayed and sustained increase in their synovial contents. In general, cytokine amounts increased earlier and more importantly in arthritic knees than in contralateral salineinjected knees, although some mediators, such as IP-10, IL-12p70, TNFa, or IL-5, PXD101MedChemExpress Belinostat failed to be affected significantly PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25112874 by the arthritic process. A similar lack of change was noted for the growth factors G-CSF and GM-CSF in all biological fluids, whereas a marginal decrease of IL-4 and IL-10 levels was observed.Cytokines with an early release in arthritic fluidAs early as 7 hours after arthritis induction, the amounts of the proinflammatory cytokines IL-1b and IL-6 increased by 12- and 55-fold, respectively, in the SF of sensitized joints (Figure 5a,c). However, IL-1 isoforms displayed a distinct pattern of evolution since IL-1b levels remained significantly elevated in arthritic joints until D 14 (Figure 5a) whereas IL-1a declined progressively (Figure 2). The intra-articular peaks of mediators averaged 150 pg/knee for IL-6 and 45 pg/knee for IL-1b (Figure 5a,c), but no significant variation was noted in corresponding sera. In arthritic fluid, the level of IL-18 and IL-13 increased only from D 2 and D 7 (2-fold increase) until D14 (3- and 4-fold increases), respectively (Figure 5b,d). However, an unexpected 2.2-fold increase in IL-18 level was observed in the contralateral knee from D1 to D2 after the antigenic challenge (Figure 5b). Such variation was consistent with the transient release of IL-18 into the bloodstream by D1.Expression profile of selected growth factorsThe amounts of the chemokines MIP-1a, MCP-1, GRO/ KC, eotaxin, and RANTES increased by 9-, 14-, 14-, 2-, and 2-fold, respectively, in the SF of arthritic rats within 7 hours after the antigenic challenge (Figure 2). No significant changes were observed in the SF of the contralateral knee. In sera, GRO/KC, MCP-1, and RANTES levels were also increased, although the range of induction remained limited (2.7-, 2-, and 1.8-fold, respectively) since these chemokines displayed a high circulating level under basal conditions (Figure 3a,b,c). The intra-articular peaks of mediator averaged 60 pg/knee for MCP-1 (Figure 3a), 45 pg/knee for GRO/KC (Figure 3b), 15 pg/knee for RANTES (Figure 3c), and 5 pg/knee for eotaxin (Figure 3d). These chemokines returned to basal levels in arthritic fluids and sera within D3, but a secondary flare of RANTES release (2-fold change) was observed on D14. The immunomodulatory cytokines IL-17 and IFNg increased by 25- and 21-fold, respectively, in the SF of arthritic rats within 7 hours after the antigenic challenge (Figure 4a,c). However, both cytokines displayed a different time course.
