Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet.

OBJECTIVE: C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP (hCRP)-transgenic mouse model whether CRP itself contributes to the development of 'metabolic' OA. DESIGN: Metabolic OA was induced by feeding 12-week-old hCRP-transgenic males (hCRP-tg, n = 30) and wild-type littermates (n = 15) a 45 kcal% high-fat diet (HFD) for 38 weeks. Cartilage degradation, osteophytes and synovitis were graded on Safranin O-stained histological knee joint sections. Inflammatory status was assessed by plasma lipid profiling, flow cytometric analyses of blood immune cell populations and immunohistochemical staining of synovial macrophage subsets. RESULTS: Male hCRP-tg mice showed aggravated OA severity and increased osteophytosis compared with their wild-type littermates. Both classical and non-classical monocytes showed increased expression of CCR2 and CD86 in hCRP-tg males. HFD-induced effects were evident for nearly all lipids measured and indicated a similar low-grade systemic inflammation for both genotypes. Synovitis scores and synovial macrophage subsets were similar in the two groups. CONCLUSIONS: Human CRP expression in a background of HFD-induced metabolic dysfunction resulted in the aggravation of OA through increased cartilage degeneration and osteophytosis. Increased recruitment of classical and non-classical monocytes might be a mechanism of action through which CRP is involved in aggravating this process. These findings suggest interventions selectively directed against CRP activity could ameliorate metabolic OA development.

Massive hemoptysis: control by transcatheter bronchial artery embolization.

Massive hemoptysis (600 ml in 48 hours) has an ominous prognosis with a mortality of 50 to 100% in medically treated patients and up to 35% in patients undergoing operation. Surgical resection has been the procedure of choice in patients with massive hemoptysis. Those with a contraindication to operation present a particularly frustrating problem. We have treated 7 such patients with massive hemoptysis by transcatheter bronchial artery embolization. In all 7, the bleeding was arrested. Two patients died of recurrent hemoptysis, 1 ten days and the other 2 months following embolization, and 5 are well 1 month to one year later. Transcatheter bronchial artery embolization is a valuable therapeutic modality in patients with massive hemoptysis. However, the procedure is palliative, and, therefore, elective resection must be considered as definitive treatment in those patients who have no contraindication to operation.