Interleukin 2 production and responsiveness in active and inactive rheumatoid arthritis

The interleukin 2 (IL-2) production and responsiveness of peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) with active or inactive disease was compared with that of normal control donors. IL-2 production was assessed using a cellular interleukin assay in which an IL-2 dependent cell line was cocultured with varying numbers of irradiated IL-2 producing lymphocytes from the different donor sources. Cells from patients with active disease showed a significantly different pattern of IL-2 production from that of control or inactive RA patients in that a lower number of cells supported growth of the IL-2 dependent cell line. In one patient this shift in pattern was shown to correlate with change in disease activity. Lymphocyte responsiveness to IL-2 as determined by limiting dilution analysis did not differ significantly between the different groups. The results are consistent with a hyperproduction of IL-2 in RA during active disease.     

Bone mineral density in patients with recently diagnosed, active rheumatoid arthritis

OBJECTIVES: Osteoporosis is a well-known extra-articular phenomenon in patients with uncontrolled, long-standing rheumatoid arthritis (RA). In the present study, the extent of osteoporosis and reduced bone mineral density (BMD) and the disease-related and demographic factors that are associated with osteoporosis and reduced BMD were examined in patients with recently diagnosed, active RA. METHODS: BMD of the total hip and the lumbar spine was measured using dual-energy x ray absorptiometry in 381 patients with recently diagnosed active RA, who had never been treated with DMARDs or corticosteroids. Osteoporosis was defined as a T score 相似文献   

Ventricular function abnormalities in active rheumatoid arthritis: a Doppler echocardiographic study

Objective The aim of the present study was to evaluate cardiac involvement in patients with active rheumatoid arthritis (RA).Methods Forty patients with active RA participated. All were submitted to standard Doppler echocardiography and myocardial performance index (MPI) grading.Results There were left and right ventricular diastolic function abnormalities in RA patients. Left ventricular MPI was also significantly higher than in controls (P<0.05). A relationship was found between left ventricular early diastolic (E)/atrial (A) flow velocities (E/A ratio), isovolumic relaxation time (IRT), and disease duration (r=–0.47 and P=0.002, r=0.618 and P=0.000, respectively).Conclusion Diastolic function was impaired in both ventricles in patients with active RA. There was a direct relationship between some of the parameters of left ventricular diastolic function and disease duration as well. These findings suggest a subclinical myocardial involvement in RA patients.     

Interleukin 6 in the physiopathology of rheumatoid arthritis

Interleukin (IL) 6 was identified in 1986 as a factor produced by T lymphocytes, that mediates growth and immunoglobulin synthesis on B lymphocytes. IL-6 is a member of a large cytokine family sharing a gp130 membrane receptor. This receptor mediates specific Jak/STAT3 activation, which induces widespread expression of pro-inflammatory and immunoregulatory genes. IL-6 mediates potent systemic responses, in organs distant from its local inflammatory sources, in a prominent fashion compared to other cytokines. Most specific effects involve hematopoiesis and hepatic acute phase reactants synthesis. IL-6 became a rheumatoid arthritis (RA) target due to its pro-inflammatory and joint destructive potential, as well as its participation in T and B immunoregulation. The therapeutic success of tocilizumab has confirmed IL-6 as an RA target. Although additional studies on the participation of IL-6 in RA physiopathology are needed, a number of indirect data point to a relevant position in this setting.     

Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease

OBJECTIVE: To investigate sympathetic (SNS) and parasympathetic (PNS) nervous system activity in patients with recently diagnosed rheumatoid arthritis (RA), and to analyze the association between activity of these systems and disease activity, and complaints that frequently occur in RA, viz., pain, fatigue, negative mood, and stiffness. METHODS: To assess sympathetic and parasympathetic nervous activity, the Pre-Ejection-Period (PEP) and Respiratory Sinus arrhythmia (RSA) were measured on two consecutive nights in a real-life environment in 25 patients with RA [19 female (f), 6 male (m), mean age 55.2 years) and 28 healthy controls (20f, 8m, mean age 55.8 years]. RESULTS: Patients showed a significantly shorter PEP (reflecting elevated SNS activity) compared to healthy controls, an effect that was most pronounced in those with active disease. RSA and the heart period did not differ between patients and healthy controls. The heart period was significantly associated with stiffness, but neither PEP nor RSA were associated with pain, fatigue, mood, or stiffness. CONCLUSION: Our study showed that cardiac sympathetic nervous system activity is elevated in RA, whereas cardiac parasympathetic activity remains at a normal level. Our results suggest that inflammatory stress rather than the common symptoms of RA challenge the SNS.     

Minocycline in active rheumatoid arthritis

Objective. To determine the efficacy of minocycline in the treatment of rheumatoid arthritis (RA). Methods. Minocycline (maximal oral daily dose 200 mg) or placebo was administered in a 26-week, randomized, double-blind study to 80 patients with active RA, who were treated or had previously been treated with at least one disease-modifying antirheumatic drug. Results. There were 15 premature discontinuations: 6 (5 taking minocycline) because of adverse effects, 8 (all taking placebo) because of lack of efficacy, and 1 (taking placebo) because of intercurrent illness. There was a statistically significant improvement in the minocycline group over the placebo group. There was a pronounced improvement in laboratory parameters of disease activity; however, improvement in clinical parameters was less impressive. The observed adverse effects attributable to minocycline were mainly gastrointestinal symptoms and dizziness. Conclusion. The results of the present study suggest that minocycline is beneficial and relatively safe in RA patients.     

Infliximab in active early rheumatoid arthritis

Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA).     

Liver abnormalities in penicillamine treated rheumatoid arthritis.

Liver enzymes were followed in 99 patients treated with D-penicillamine for rheumatoid arthritis. In six abnormalities were found which consisted of elevated levels of lactic dehydrogenase. ALAT/ASAT, alkaline phosphatases or combinations of these. The changes were reversible on stopping the drug with one possible exception. No evidence of biliary cirrhosis, chronic active hepatitis or HBag-associated hepatitis was found. Liver biopsy was performed in 4 cases--one was taken 2 months after the treatment was discontinued, and was normal. One biopsy showed mild inflammatory changes, whereas in two histologic evidence of toxic liver necrosis was present. Liver damage should be included among possible complications of D-PA treatment.     

Changing patterns of pulmonary abnormalities in rheumatoid arthritis

BackgroundAs a first step in identifying the developmental pathways of pulmonary abnormalities in rheumatoid arthritis (RA), we sought to determine the existing and changing patterns of pulmonary abnormalities.MethodsWe conducted a retrospective cohort study of consecutive patients with RA who underwent high-resolution computed tomography before and during biologic therapy. The presence of 20 pulmonary abnormalities and the changes in those abnormalities were recorded. Patterns of pre-existing and changing abnormalities were examined via cluster analysis, and their relationship was also assessed using the Kaplan–Meier method and log-rank test.ResultsA total of 208 subjects were included. Pulmonary abnormalities were observed in 70% of patients: 39% had interstitial lung disease, and 55% had airway disease (AD). Several different pulmonary abnormalities were commonly found to co-exist in several patterns in the same patient. In most patients with pulmonary abnormalities, AD was present alone or in combination with other abnormalities. During the observation period (mean 3.2 years), 172 pulmonary abnormalities had changed in 91 patients: 115 pulmonary abnormalities newly emerged, whereas 42 worsened and 25 demonstrated improvement. Pulmonary abnormalities changed in several patterns. Correlations were observed between pre-existing and new/worsening abnormalities at individual and regional levels, such as new ground-glass opacity (GGO) and pre-existing AD, small nodular patterns, and honeycombing. AD was a possible initial abnormality.ConclusionsPulmonary abnormalities occurred and changed in several patterns, which suggests the existence of developmental pathways of pulmonary abnormalities. AD may play an important role in the development of these abnormalities, including GGO.     

The prevalence of coagulation abnormalities in juvenile rheumatoid arthritis

To determine the prevalence of coagulopathy in juvenile rheumatoid arthritis, results of repeated coagulation studies obtained on 73 patients over one year were correlated with disease activity, liver function abnormalities and drug therapy. In spite of active and severe disease in the majority of these children, coagulation abnormalities developed in only 2 cases and there was no instance of clinically apparent bleeding. Although these results suggest that the development of coagulopathy is uncommon, the physician must continue to exercise vigilance for this potentially life threatening complication, especially when caring for the child with systemic disease receiving combinations of drug therapy.