Serum analysis of cytokines revealed up regulation of several cytokines in the arthritic mice compared with the non-arthritic mice, and treatment with IL-17 antibody and celecoxib completely prevented formation of lung metastasis in the SKG mice. (a) Array template of the cytokines on the membrane. Up-regulation of macrophage colony stimulating factor (M-CSF), TNF-alpha, IL-17, vascular endothelial growth factor (VegF), and IL-6 is observed and highlighted in gray on the template (b to g) Membrane dot blot representing circulating cytokine levels in various groups of mice (indicated in the Figure). Boxes are drawn around the cytokines that were up-regulated. (h) A graphical representation of the up-regulated cytokines observed on the membrane blots based on densitometry analysis (n = 4 mice). (i) Significant reduction in tumor burden in mice treated with celecoxib (P < 0.05), α-IL-17 antibody (P < 0.01) or α-IL-17 antibody + celecoxib (P < 0.01) as compared with the untreated or IgG isotype group; (j) Percentage of mice that developed lung metastasis. (k) Schematic model depicting the vicious interaction between metastatic breast tumors and the inflammatory microenvironment in the bone and lung due to autoimmune arthritis (AA). During arthritis, inflammatory cell infiltrate in the bones and lungs trigger the release of pro-inflammatory cytokines. These cytokines act directly or indirectly on the primary breast tumor cells enhancing their metastatic ability. The ensuing damage to the bones and the large amounts of inflammatory cells in the bones and lungs of the arthritic mice allows retention and growth of the tumor cells in the site. The final distribution of metastasis reflects the relative abundance of inflammation in the organs. Thus, we hypothesize that the increase in some of the proinflammatory cytokines such as IL-17 may be the underlying factor responsible for the increased metastasis.