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 −25% versus 9%; nitrotyrosine −38% versus −11%; interleukin-6 −29% versus 0.9%; endothelin-1 −36% versus −11%; flow-mediated dilation 45% versus −9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%;P<0.05 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 (P<0.05).Conclusions—Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.

During life, bone undergoes modelling and remodelling in order to grow or change shape. Bone modelling is the process by which bones change shape or size in response to physiologic influences or mechanical forces that are encountered by the skeleton, while bone remodelling takes place so that bone may maintain its strength and mineral homeostasis. During early childhood, both bone modelling (the formation and shaping of bone) and bone remodelling (the replacement or renewal of old bone) occur. The predominant process in childhood is bone modelling, while in adulthood bone remodelling predominates. The exception to this is after a fracture when we see massive increases in bone formation. During childhood and adolescence growth occurs in the bones longitudinally and radially, while in the growth plates it occurs longitudinally, thus promoting growth in size. Cartilage first proliferates in the epiphyseal and metaphyseal areas of long bones before undergoing mineralisation to form new bone.

Background—: We investigated the effects of anakinra, an interleukin-1 receptor antagonist, on coronary and left ventricular function in coronary artery disease (CAD) patients with rheumatoid arthritis.Methods and Results—: In a double-blind crossover trial, 80 patients with rheumatoid arthritis (60 with CAD and 20 without) were randomized to a single injection of anakinra or placebo and after 48 hours to the alternative treatment. At baseline and 3 hours after treatment, we assessed (1) flow-mediated dilation of brachial artery; (2) coronary flow reserve, ejection fraction, systemic arterial compliance, and resistance by echocardiography; (3) left ventricular global longitudinal and circumferential strain, peak twisting, untwisting velocity by speckle tracking; and (4) interleukin-1β, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1β, protein carbonyl, higher nitrotyrosine, malondialdehyde, and Fas/Fas ligand than non-CAD (P<0.05). After anakinra, there was a greater improvement of flow-mediated dilation (57±4% versus 47±5%), coronary flow reserve (37±4% versus 29±2%), arterial compliance (20±18% versus 2±17%), resistance (−11±19% versus 9±21%), longitudinal strain (33±5% versus 18±2%), circumferential strain (22±5% versus 13±5%), peak twisting (30±5% versus 12±5%), untwisting velocity (23±5% versus 13±5%), ejection fraction (12±5% versus 0.5±5%), apoptotic and oxidative markers, and, in particular, of protein carbonyl (35±20% versus 14±9%) in CAD than in non-CAD patients (P<0.01). No changes in the examined markers were observed after placebo.Conclusions—: Interleukin-1 inhibition causes a greater improvement in endothelial, coronary aortic function in addition to left ventricular myocardial deformation and twisting in rheumatoid arthritis patients with CAD than in those without.Clinical Trial Registration—: URL:http://www.clinicaltrials.gov. Unique identifier: NCT01566201.

Objective. The reciprocal relationship between systemic lupus erythematosus (SLE) and pregnancy was investigated in a controlled study. Method. The outcome of 47 pregnant SLE patients with 59 pregnancies was compared with that of 57 healthy control women and 59 pregnancies. The results were also compared with those of 59 non‐pregnant control SLE patients. Results. All pregnant SLE patients but one were in remission at the onset of pregnancy and were being treated with low doses of prednisone (≤10 mg/day, 26 patients), hydroxychloroquine (200 mg/day, eight patients) or azathioprine (100 mg/day, one patient). Sixty‐one per cent of SLE pregnancies were delivered at term and 5% had premature deliveries. The rates of spontaneous abortion and total fetal loss were significantly higher in the mothers with SLE than in the control population (P < 0.001 and P < 0.01 respectively). None of the 39 neonates from SLE mothers had neonatal lupus, anti‐Ro(SSA) or anti‐La(SSB) antibodies. Eight out of 59 pregnancies of SLE mothers (13.5%) were characterized by disease exacerbation. Arthralgias or arthritis, fever and skin lesions were observed more frequently in the mothers with SLE than in the non‐pregnant group (P < 0.001). Renal involvement was found in three SLE patients during pregnancy and in three after delivery. Conclusions. Pregnant women with SLE are at high risk of fetal loss and spontaneous abortion. Pregnancy does not cause life‐threatening manifestations of the disease. Thus, for a better outcome of lupus pregnancy, it is essential to control disease activity and to achieve clinical remission.

We investigated whether gender and age influence the clinical course and outcome in systemic lupus erythematosus (SLE) patients. Thus, we analyzed the clinical and laboratory data of 489 SLE patients at presentation and during follow-up. In addition, disease activity score (using the European Consensus Lupus Activity Measure, ECLAM) and organ damage index (using the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index, DI) were measured. Furthermore, data from both sexes were analyzed according to the following age groups: < 55 years (younger group) and > 55 years (older group). There were 68 men and 421 women, giving a ratio of 1:7. We found no differences in the mean age, mean age at diagnosis, disease duration as well as duration of follow-up between men and women. Young men presented more frequently with serositis and discoid lesions, while women presented with Raynaud's phenomenon (RP) and malar rash. Regarding the laboratory findings, young women presented more often with anti-Ro(SSA) and anti-La(SSB) antibodies, while increased levels of erythrocyte sedimentation rate (ESR) were found in old women. During follow-up, men had serositis and renal disease more frequently, while the women's group were found to complain of RP, photosensitivity and mucosal ulcers more frequently, especially in young women. Anemia, leukopenia, thrombocytopenia and elevated levels of ESR were also found more frequently in young women during follow-up. However, there were no significant differences concerning ECLAM and DI scores between the two gender groups. Using multiple logistic regression analysis, a statistically significant association of malar rash, discoid lesions, serositis, RP, anti-Ro(SSA)= La(SSB) and increased ESR with sex was found independently of age, while only malar rash showed a statistically significant association with age independentlyof sex. Thus, we conclude that gender influences the clinical expression of the disease independentlyof age, while both gender and age do not affect the overall damage score.