Endogenous IL-11 is pro-inflammatory in acute methylated bovine serum albumin/interleukin-1-induced (mBSA/IL-1)arthritis

OBJECTIVE: To evaluate the role of interleukin-11 (IL-11) in acute mBSA/IL-1-induced inflammatory arthritis. METHODS: IL-11 was administered via intra-articular (IA) injection into knee joints of C57BL/6 mice and joint histology was assessed. The mitogenic response to IL-11 was measured in wild-type (WT) synovial fibroblasts. IL-1 was used as a comparator in both the studies. The severity of acute methylated bovine serum albumin (mBSA)/IL-1 arthritis was determined in WT and IL-11 receptor null (IL-11Ra1-/-) mice. In parallel experiments, a neutralising antibody to IL-11 was administered to WT mice throughout this model. RESULTS: IA injections of IL-11 resulted in mild-to-moderate joint inflammation which was less than that due to IA IL-1. IL-11 had a dose-dependent mitogenic effect on WT synovial fibroblasts (P<0.01). mBSA/IL-1 acute arthritis was reduced in IL-11Ra1-/- versus WT mice (histological arthritis score: 10.1+/-0.5 versus 12.8+/-0.7, respectively; P=0.01). Administration of an IL-11 neutralising antibody to WT mice reduced mBSA/IL-1 acute arthritis scores compared to control antibody (10.6+/-0.7 versus 13.3+/-0.6, respectively; P=0.02). CONCLUSIONS: These data demonstrate that endogenous IL-11 exerts relatively mild but consistent pro-inflammatory effects in acute inflammatory arthritis.