Anti-inflammatory effects of ERT and combined ERT/anti-TNF-alpha therapy in MPS VI rats.

<p>(<b>A</b>) MPS VI rats were subjected to the ERT (black) or combined ERT/anti-TNF-alpha (gray) treatment for 8 months, as described in the text (n = 8/group). The animals were euthanized 2 days after the last injection and serum was collected. Age-matched (37 weeks) normal (light gray) and untreated MPS VI (white) sera also were collected, and TNF-alpha and RANKL levels were determined using immunoassay kits (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022447#s2" target="_blank">Materials and Methods</a>). As previously shown, untreated MPS VI animals had markedly elevated levels of these two inflammatory markers, and both were significantly reduced by either ERT or combined treatment (*p<0.005). No significant differences were observed between the two treatment protocols. (<b>B</b>) Untreated MPS VI rats exhibited markedly elevated TNF-alpha immunostaining (red) in the articular cartilage as compared to normal animals, which was modestly reduced by ERT and normalized by combined treatment. (<b>C</b>) Hyperplastic synovial membranes (*) with the formation of villi (SV), and invasion of the synovium into the subchondral bone (arrowhead, SB) was evident in untreated MPS VI and ERT-treated synovium. Animals treated with combined therapy exhibited markedly less joint inflammation, although the storage cells were still present.