Serum zinc and copper levels and serum interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) levels were evaluated in 57 female patients with active rheumatoid arthritis (RA) to investigate a possible role of IL1 beta and TNF alpha on zinc and copper homeostasis in RA. Serum zinc levels were significantly lower and serum copper levels significantly higher in RA patients when compared with osteoarthritis or asymmetrical psoriatic oligoarthritis patients and with normal controls. No differences were observed in serum IgM rheumatoid factor positive and serum IgM rheumatoid factor negative patients as regards serum zinc and copper concentration. In RA patients the erythrocyte sedimentation rate and acute-phase proteins correlated negatively with serum zinc and positively with serum copper. IL1 beta and TNF alpha were found to correlate negatively with zinc and positively with copper in RA patients. Lower levels of zinc may be due to an accumulation of zinc-containing proteins in the liver and in the inflamed joints in RA. Elevated serum copper levels seem to be linked to the increased synthesis of ceruloplasmin by the liver.

Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1 beta and TNF-alpha circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1 beta and TNF-alpha levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1 beta and TNF-alpha reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients.

Cytokines 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.

Androgen 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 IL1beta 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 mu mol/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). IL1beta 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.

SUMMARY 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.Dietary composition has been shown to influence the immune response both in animals and in humans.' Therefore dietary manipulations may form the basis for a nutritional approach to treating autoimmune disorders.The regulatory effect of dietary lipid composition on many biological processes is well known.24 The ratio polyunsaturated:saturated fatty acids (P:S ratio) and the n-3 fatty acid amount are the important factors. Whereas the P:S ratio regulates the concentration of plasma cholesterol,S the n-3 fatty acids (eicosapentaenoate 20:5, docosahexaenoate 22:6) are mainly involved in the regulation of arachidonate metabolism.6The main source of eicosapentaenoic acid and docosahexaenoic acid is fish derived oil and an adequate dietary content seems to be 2-5 g/day.The relation between dietary factors and rheumatoid arthritis is becoming more evident.7 8 Furthermore, patients with rheumatoid arthritis (RA) show a notable increase of arachidonate metabolism via lipoxygenase, leading to leucotrienes B4 or D4.9Recently, Lee et al presented evidence for an inhibitory effect on polymorphonuclear activity of a diet rich in n-3 fatty acids.10