Altomonte L

Serum levels of interleukin-1b, tumour necrosis factor-a and interleukin-2 in rheumatoid arthritis. Correlation with disease activity

SummaryCytokines are potent immunoregulatory factors and may be directly involved in the disordered immunoregulation found in chronic rheumatic diseases. Interleukin-1b (IL-1b), Interleukin-2 (IL-2) and Tumour Necrosis Factor-a (TNF-a) have been implicated in the pathogenesis of rheumatoid arthritis (RA) as mediators of chronic inflammation. Serum levels of IL-1b and TNF-a measured by radioimmunoassay were significantly higher in patients with RA than in healthy controls of similar sex and age while serum levels of IL-2 were significantly lower in the same patients. Further IL-1b and TNF-a were significantly elevated in RA patients with active disease and IL-2 was significantly reduced when compared with patients with low active disease. Serum IL-1b and TNF-a appear to correlate with systemic inflammation, and systemic features of RA may result from dissemination of cytokines produced in the synovium. The role of IL-2 in RA remains controversial. Reduced levels of IL-2 may be an expression of a deficiency of T-cells to produce IL-2 in the active phases of RA or may be due to a possible absorption of IL-2 by lymphocyte receptors.

A study of serum androgen and cortisol levels in female patients with rheumatoid arthritis. Correlation with disease activity

SummaryAndrogen status and the role played by androgens in the pathogenesis of rheumatoid arthritis (RA) in female patients are a matter of debate. In the present study serum testosterone (T), DHEAS, sex hormone binding globulin (SHBG) and cortisol levels were determined in 55 RA women, both in pre- and post-menopausal (M) status, and in a group of healthy subjects. Patients were divided into two groups according to disease activity and a correlation analysis of hormonal levels against serum IL1β levels was performed. No significant differences were found in serum T levels between RA patients and controls, both in preM (1.38±0.4 vs 1.35±0.3 nmol/l; p=ns) and in postM status (1.21±0.2 vs 1.10±0.2 nmol/l; p=ns). Serum SHBG levels were lower in RA patients than in control subjects, both in pre and in postM status. DHEAS levels were significantly lower in preM RA patients than in controls (2.34±1.2 vs 5.93±1.6 µmol/l; p<0.001) while cortisol levels were significantly higher in preM active RA patients than in controls (466.2±30.3 vs 411±66.2 nmol/l; p=0.02). IL1β levels were significantly higher in RA patients than in controls both in pre- and postM subjects (70±33.8 vs 23.1±2.9 and 92±27.4 vs 31.9±3.1 fmol/l, p<0.001, respectively).Although androgen status could play a role in the pathogenesis of RA, at present it is not possible to exclude the influence of RA itself on sex hormone profile.

Influence of diet with different lipid composition on neutrophil chemiluminescence and disease activity in patients with rheumatoid arthritis.

Neutrophil chemiluminescence was determined in patients with active rheumatoid arthritis. Twelve patients were randomly assigned either to a diet high in polyunsaturated fatty acids supplemented with eicosapentaenoic and docosahexaenoic acids or to a diet high in saturated fatty acids. A correlation with clinical and laboratory parameters is also reported. No statistical difference was observed in neutrophil chemiluminescence and in clinical parameters in the group of patients treated with a diet high in saturated fatty acids. Fish oil ingestion resulted in subjective alleviation of active rheumatoid arthritis and reduction of neutrophil chemiluminescence. This study corroborates the hypothesis of an anti-inflammatory role for polyunsaturated fatty acids in patients with chronic inflammatory diseases.

Clinically silent inflammatory gut lesions in undifferentiated spondyloarthropathies

SummaryGastrointestinal inflammation or infection can be associated with various forms of arthritis, such as, acute reactive arthritis triggered by enteritis due to gram-negative bacteria or ankylosing spondylitis and peripheral arthritis in relation to Crohns disease and ulcerative colitis. Using colonoscopy, we have found a high prevalence of clinically silent inflammatory lesions in 38 patients (24 males and 14 females) affected by undifferentiated spondyloarthropathies (SpA). Microscopic inflammatory lesions were present in all the patients. Three patterns of nonspecific chronic inflammatory alterations were observed. No difference was noted between patients taking or not taking nonsteroidal anti-inflammatory drugs. Direct immunofluorescence demonstrated the presence of IgG, IgA, IgM, C3, C4 and fibrinogen in 75% of the specimens examined. The finding of chronic inflammatory gut lesions hypothesizes that a local activation of the immune system depending on the persistence of intestinal microbial antigens or toxins, due to impaired elimination or increased exposition, may have a part in the pathogenesis of SpA.

Seronegative spondarthritis associated with Takayasu's arteritis.

A young woman presented with an aortic arch syndrome a few years after the onset of ankylosing spondylitis. Tissue typing showed HLA-B27. The possibility of an association between ankylosing spondylitis and Takayasus arteritis is suggested.

Lack of correlation between anticardiolipin antibodies and peripheral autonomic nerve involvement in systemic lupus erythematosus.

SummaryThe presence of anticardiolipin antibodies has recently been related to a clinical complex in which both central and peripheral neurologic damage is included. A series of 27 female patients affected by systemic lupus erythematosus (SLE) was tested for the presence of peripheral autonomic neuropathy and serum anticardiolipin antibody (ACA) levels were determined in each patient by ELISA. Peripheral autonomic impairment was detected in 40.7% of SLE patients and a large number (77.7%) of patients had elevated levels of ACA. No relationship was found between presence of ACA (both for IgG and IgM classes) and the autonomic neuropathy.

Effect of Fenfluramine on Growth Hormone and Prolactin Secretion in Obese Subjects

Obese subjects show a subnormal growth hormone (GH) and prolactin (PRL) release in response to a variety of stimuli. Fenfluramine, an anorexiant drug used in obesity therapy, may have some effects on hypothalamic-pituitary function mediated by serotoninergic stimulation. The present investigation in obese subjects was carried out to study the effects of fenfluramine (60 mg orally) on GH and PRL secretion after intravenous arginine infusion. Ten volunteer obese females were studied and compared with 10 volunteer normal weight controls. In the obese group the GH response to arginine was significantly lower than in control group. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. The PRL response to arginine in obese women was subnormal. Fenfluramine administration restored the response of PRL to arginine infusion to normal. In conclusion, fenfluramine--under acute circumstances--enhances the hypothalamic-pituitary response to arginine in obese subjects. The decreased GH and PRL output in obese subjects is not due to an absolute hormonal deficiency and this effect of fenfluramine on GH secretion may--due to its lipolysis stimulation--be useful in obesity treatment.

Effect of Fenfluramine on Insulin/Growth Hormone Ratio in Obese Subjects

Obesity is characterized by increased levels of insulin and by subnormal growth hormone (GH) release. Insulin/GH ratio is significantly higher in obese than in lean individuals. Fenfluramine, an anorectic drug, may have some effects on hypothalamic-pituitary function and on insulin secretion, possibly through a serotonergic stimulation. The aim of this work was to study the effects of fenfluramine on the insulin/GH ratio after arginine in obese subjects. Ten volunteer obese females were studied; 10 volunteer women were the normal weight controls. All subjects were given placebo and fenfluramine (60 mg p.o.) in a randomized order and after 120 min underwent arginine infusion (25 g i.v. for 30 min). Blood samples were taken every 30 min until 270 min for GH and insulin radioimmunoassay. In the obese group the GH response to arginine was significantly lower than in controls. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. Arginine infusion provoked a greater insulin secretion in obese subjects than in lean individuals. Fenfluramine administration diminished the insulin response to arginine. Fenfluramine did not modify the insulin/GH ratio in controls while it significantly lowered the insulin/GH ratio in obese subjects. Because insulin promotes fat and carbohydrate storage while GH stimulates lipolysis, the combination of high insulin and low GH concentrations may worsen the obese condition. A lower insulin/GH ratio can be useful in the treatment of obesity.

Effect of fish oil on neutrophil chemiluminescence induced by different stimuli in patients with rheumatoid arthritis.

Lipid composition plays an important part in the structural and metabolic functions of cell membranes. In particular the production of inflammatory mediators such as prostaglandins and leukotrienes is dependent on polyunsaturated fatty acid precursors. Neutrophil leucocytes participate in inflammatory processes by their phagocytic and killing activities which can be monitored by measuring the photon emission (chemiluminescence). Chemiluminescence was measured in a luminol dependent system after stimulation by either particulate (zymosan) or soluble (phorbol myristate acetate) stimulus in a group of 10 patients with rheumatoid arthritis before and 21 and 45 days after treatment with a diet supplemented with eicosapentaenoic and docosahexaenoic acids. Ten patients with rheumatoid arthritis continuing their usual diet were used as control subjects. A progressive reduction of chemiluminescence stimulated by zymosan and phorbol myristate acetate was found in the patients treated with fish oil supplementation. This result correlated well with the reduction in erythrocyte sedimentation rate and an improvement of clinical parameters. The effects of fish oil derived lipids on neutrophil chemiluminescence are probably due to a change of the lipid composition of the cell membrane which is dependent on the esterification of eicosapentaenoic acid and docosahexaenoic acid in cellular membrane phospholipids. The modification of membrane lipid composition seems to interact in a non-specific way with the metabolic activation of neutrophils during phagocytosis.

Serum osteocalcin as an index of bone turnover in active rheumatoid arthritis and in active psoriatic arthritis

SummaryJuxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05±1.27 ng/ml vs 4.83±0.88 ng/ml;p<0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.