Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthritis synovial fluid

Oxygen free radicals are probably involved in the pathogenesis of rheumatoid arthritis (RA). The enzymes involved in protection against oxygen free radicals and H2O2 (superoxide dismutase, catalase, and glutathione peroxidase) were measured. Superoxide dismutase was not increased, glutathione peroxidase was slightly and catalase was strongly elevated in RA synovial fluid (SF) compared with control SF. Although these enzymes are present in SF, the activities are insufficient to protect against oxygen free radicals and H2O2. In contrast to transferrin, ferritin was increased in RA synovial fluid. Ceruloplasmin was also elevated. When rat liver microsomes were used as a target for oxygen free radicals, serum and SF were both protective. Gel filtration experiments showed that the fraction pattern in which there was maximal protective potential against lipid peroxidation corresponded closely to the level of ceruloplasmin. After removal of ceruloplasmin from serum or SF, about 70% of the protective capacity disappeared. It is concluded that ceruloplasmin is an important protector against oxygen free radicals. Copyrigh

Anaemia of chronic disease in rheumatoid arthritis - Raised serum interleukin-6 (IL-6) levels and effects of IL-6 and anti-IL-6 on in vitro erythropoiesis

Serum and bone marrow from 21 patients with rheumatoid arthritis (RA) were studied in order to establish the pathogenetic role of interleukin-6 (IL-6) in anemia of chronic disease (ACD). Erythroid colony growth, using burst forming units of erythroblasts (BFUe) as a parameter, was impaired in ACD and not in nonanemic RA controls. Serum IL-6 was elevated in ACD and it correlated well with parameters of disease activity such as erythrocyte sedimentation rate and C-reactive protein. IL-6 addition to bone marrow cultures had inconsistent effects while anti-IL-6 addition resulted in impaired erythroid colony growth, suggesting stimulatory effects of IL-6 produced in the medium, which may be masked by simultaneous production of cytokines with suppressive effects. It was concluded that elevated serum IL-6 in ACD reflects disease activity. It probably plays no pathogenetic role in ACD. Its stimulatory effects on erythroid growth might counteract suppressive effects of other interleukins

Serum levels of soluble forms of T cell activation antigens CD27 and CD25 in systemic lupus erythematosus in relation with lymphocytes count and disease course

Systemic lupus erythematosus (SLE) patients are characterized by a low lymphocyte count, which is considered a specific disease marker and is related to disease activity. The membrane bound molecules CD25 and CD27 are expressed and released in a soluble CD25 (sCD25) and soluble CD27 (sCD27) form by activation of predominantly T cells. In previous studies it was claimed that sCD25 as well sCD27 might be used as parameters for activation of the immune system; a correlation between the sCD25 profile with the disease course in SLE patients was also shown. To assess the relationship between lymphocyte count and these T cell activation markers, we performed a cross-sectional and a longitudinal study. In the longitudinal study three SLE patients who were known for a long time at our outpatient clinic were studied. Both T cell markers strongly correlated with each other and formed a reflection of the disease course. In all 7 periods of exacerbation, which we observed in the 3 investigated patients, both levels increased preceding this period; however, no correlation was found with the lymphocyte count. In the cross sectional study of 69 patients with SLE, sCD25 and sCD27 levels were correlated with defined disease manifestations; sCD25 was elevated in all periods of increased disease activity. The same holds true for sCD27, with the exception of patients with nephritis in which the highest levels were observed. Both profiles of sCD25 and sCD27 were strongly correlated during the whole disease course. Our data prove that in the pathogenesis of SLE an active recruitement of unprimed and primed T cells takes place

Acute-phase response patterns in isolated hepatic perfusion with tumour necrosis factor α (TNF-α) and melphalan in patients with colorectal liver metastases

Background. In this study, we have evaluated hepatotoxicity, secondary cytokine production and hepatic acute-phase response (APR) in patients who underwent isolated hepatic perfusion (IHP) with tumour necrosis factor (TNF) α and melphalan for irresectable colorectal liver metastases. Design. An extracorporeal veno-venous bypass was used to shunt blood from the lower body and intestines to the heart. Inflow catheters were placed in the hepatic artery and portal vein, and an outflow catheter in the inferior caval vein. The liver was perfused for 60 min with 0.4 mg of TNF-α plus 1 mg kg-1 melphalan (IHP(TM) group, n = 6) or 1 mg kg-1 melphalan (IHP(M) group, n = 3). The liver was washed with macrodex before restoring vascular continuity. Results. After the washout procedure, a TNF-α peak (169 ± 38 pg mL-1) was demons