Background/Aims: Osteoclasts (OC) originate from monocytes/macrophages and play a critical role in the development of ankylosing spondylitis (AS). Receptor activator of NF-kB ligand (RANKL) is critical for the differentiation and maturation of OC from monocytes/macrophages, the underlying mechanisms of which processes have not been completely elucidated. Interleukin 4 (IL-4) attenuates the pathogenesis of AS via ill-defined mechanisms. Methods: We used a proteoglycan-induced arthritis (PGIA) model in Balb/c mice to study AS in humans. We injected IL-4 into the articular cavity and evaluated its effects on PGIA by incidence of arthritis, clinical and pathological arthritis severity and PET tracer uptake. We isolated and analyzed the number and polarization of macrophages in the articular cavity before and after IL-4 treatment. We analyzed RANKL levels in macrophage subtypes. We then isolated bone-marrow derived macrophages and treated them with IL-4 in vitro, with or without histone deacetylase inhibitors trichostatin A (TSA), and then analyzed the polarization of cultured macrophages before and after IL-4 treatment and RANKL levels in macrophage subtypes. Results: IL-4 treatment decreased the incidence and severity of arthritis in a mouse AS model, and polarized macrophages from a classical M1 subtype to an M2 subtype in vivo and in vitro. RANKL was predominantly produced by M1, but not by M2 macrophages. IL-4-mediated inhibition of RANKL in macrophages was abolished by TSA. Conclusion: Our data suggest that the therapeutic effects of IL-4 on AS may result from a M1-to-M2 macrophage polarization and its inhibition of RANKL expression on macrophages, possibly through enhanced histone deacetylation.

The purpose of this study is to evaluate the potential benefits of rib fracture fixation in patients with flail chest and multiple non-flail rib fractures versus conventional treatment modalities. A retrospective reviewed study compared 86 cases which received surgical treatment between June 2009 and May 2013 to 76 cases which received conservative treatment between January 2006 and May 2009. The patients were divided into the flail chest (n=38) and multiple non-flail rib fracture groups (n=124). In the flail chest group, the mechanical ventilation time, ICU monitoring time, tracheostomies, thoracic deformity, and impaired pulmonary function and return to full-time employment were compared. In the multiple non-flail rib fracture group, fracture healing, visual analog scale (VAS) pain score, inpatient length of stay, atelectatic, pulmonary complications, and normal activity-returning time were compared. Patients in the flail chest operative fixation group had significantly shorter ICU stay, decreased ventilator requirements, fewer tracheostomies, less thoracic deformity and impaired pulmonary function, and more returned to fulltime employment. Patients in the multiple non-flail rib fracture operative fixation had shorter hospital stay, less pain, earlier return to normal activity, more fracture healing, less atelectasis, and fewer pulmonary infections. This study demonstrates the potential benefits of surgical stabilization of flail chest and multiple non-flail rib fractures with plate fixation. When compared with conventional conservative management, operatively managed patients demonstrated improved clinical outcomes.

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