Arthritis was induced in male and female mice by i.p. that the transgenic model did not require LPS at all for arthritis development but a lower dose of LPS (10 g) was found necessary for reproducible and robust disease (close to 100% incidence, well-synchronised, with high arthritis scores). Furthermore the LPS challenge could be brought forward to Day 1 so that its actions to facilitate disease could be separated temporally from the arthritis phase (beginning about Day 4). Etanercept, administered immediately after the serum spike of cytokines associated with LPS had subsided, was able to dose-dependently inhibit arthritis development and this was associated with a marked protection of the joints histologically on Day 14. Etanercept was also able to reverse the signs of arthritis when given therapeutically allowing animals to be matched for disease burden before dosing begins. Conclusions The features of CAIA in Tg1278TNFko animals make the model well-suited to testing the next generation of therapeutics that will target human TNF in rheumatoid arthritis. Keywords: Collagen antibody induced arthritis, Rheumatoid arthritis, Tg1278TNFko mice, TNF Background In recent years the treatment of rheumatoid arthritis (RA) has been transformed by the development of biologics targeting tumour necrosis factor alpha (TNF). Response rates to treatment, as assessed by American College of Rheumatology (ACR) criteria, are typically in the region of 60% ACR20, 40% ACR50 and 20% ACR70 at 24 weeks of treatment [1]. However biologics are expensive INSL4 antibody and so are not as widely used as they might be. Typically patients will have failed conventional treatments such as methotrexate before being considered suitable for anti TNF therapy. The problem with this is that anti TNF treatment might be more effective if initiated early, and indeed current thinking is to identify and treat RA patients as quickly as possible in an attempt to induce long term remission [2]. Another problem with biologics is that they are inconvenient to administer when compared with conventional therapy. One view of biological agents directed towards TNF is that they have validated TNF as a target for the treatment of RA but that Edrophonium chloride they will be superseded by small molecules that act on the same pathway. These treatments may be cheaper, more convenient to administer and suitable as first line Edrophonium chloride therapy either alone or in combination with other anti-rheumatic drugs such as methotrexate. Despite the success of anti TNFs in the treatment of RA, most of the preclinical work directed against TNF was to support sepsis as a disease indication [3]. Unfortunately anti TNFs proved to be a spectacular failure in sepsis. However, subsequent work Edrophonium chloride in the human TNF Tg197 transgenic mouse model of arthritis supported the therapeutic potential of anti-human TNF in RA [4] that was later confirmed by a small trial in RA [5]. It is interesting to speculate on whether anti TNFs would ever have reached the clinic for RA if preclinical development had been through conventional models such as collagen induced arthritis (CIA) in rodents. Targeting TNF, although effective to some extent in CIA, is rather less active than targeting IL-1 [6, 7] which is actually the reverse of Edrophonium chloride the clinical findings. CIA is also time consuming and suffers from variable incidence and severity. So CIA cannot be considered an ideal model for the testing of the next generation of TNF inhibitors. Because TNF is an effector cytokine, playing a role in inflammation.