Background-Interleukin-1 increases nitrooxidative stress. We investigated the effects of a human recombinant interleukin-1a receptor antagonist (anakinra) on nitrooxidative stress and vascular and left ventricular function. Methods and Results-In an acute, double-blind trial, 23 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150 mg SC) or placebo and, after 48 hours, the alternative treatment. At baseline and 3 hours after the injection, we assessed (1) coronary flow reserve, aortic distensibility, systolic and diastolic (Em) velocity of the mitral annulus, and E to Em ratio (E/Em) using echocardiography; (2) flow-mediated, endothelium-dependent dilation of the brachial artery; and (3) malondialdehyde, nitrotyrosine, interleukin-6, endothelin-1, and C-reactive protein.In a chronic, nonrandomized trial, 23 patients received anakinra and 19 received prednisolone for 30 days, after which all indices were reassessed. Compared with baseline, there was a greater reduction in malondialdehyde, nitrotyrosine, interleukin-6, and endothelin-1 and a greater increase in flow-mediated dilation, coronary flow reserve, aortic distensibility, systolic velocity of mitral annulus, and E/Em after anakinra than after placebo (malondialdehyde Ϫ25% versus 9%; nitrotyrosine Ϫ38% versus Ϫ11%; interleukin-6 Ϫ29% versus 0.9%; endothelin-1 Ϫ36% versus Ϫ11%; flow-mediated dilation 45% versus Ϫ9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%; PϽ0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (PϽ0.05). Conclusions

Infrared imaging analysis of iliac crest biopsy specimens from patients with osteoporotic and multiple spontaneous fractures shows significant differences in the spatial variation of the nonreducible: reducible collagen cross-links at bone-forming trabecular surfaces compared with normal bone.Introduction: Although the role of BMC and bone mineral quality in determining fracture risk has been extensively studied, considerably less attention has been paid to the quality of collagen in fragile bone. Materials and Methods: In this study, the technique of Fourier transform infrared imaging (FTIRI) was used to determine the ratio of nonreducible:reducible cross-links, in 2-to 4-m-thick sections, from human iliac crest biopsy specimens (N ϭ 27) at bone-forming trabecular surfaces. The biopsy specimens were obtained from patients that had been diagnosed as high-or low-turnover osteoporosis, as well as premenopausal women Ͻ40 years of age, with normal BMD and biochemistry, who suffered multiple spontaneous fractures. The obtained values were compared with previously published analyses of trabecular bone from normal non-osteoporotic subjects (N ϭ 14, 6 males and 8 females; age range, 51-70 years). Results and Conclusions: Collagen cross-links distribution within the first 50 m at forming trabecular surfaces in patients with fragile bone was markedly different compared with normal bone.

Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.