The aim of our study was to assess the levels of growth factors and interleukin (IL)-6 across the pulmonary circulation in patients with pulmonary arterial hypertension (PAH) and correlate them with clinical and haemodynamic data and outcome.Simultaneous arterial and pulmonary arterial blood samples in patients with PAH (n544) and controls (n520) were obtained during right heart catheterisation. Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-b1 and IL-6 were measured using ELISA.Arterial median (interquartile range) values for VEGF, PDGF-BB, TGF-b1 and IL-6 were significantly higher in patients (377 (218-588) versus 9.0 pg?mL , respectively; p,0.001 for all variables). There was a consistent step-up of VEGF, PDGF-BB and TGF-b1 across the lungs in PAH patients (p,0.001, p50.002 and p,0.001, respectively), whereas in controls, arterial and pulmonary arterial serum levels of IL-6 and growth factors were similar (statistically nonsignificant). In multivariate analysis, increased IL-6 levels predicted mortality (hazard ratio 1.08 (95% confidence interval 1.02-1.15); p50.012).Our findings indicate increased release and/or decreased clearance of growth factors at the lung vascular level, which may contribute to vascular remodelling in PAH.

Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.

Objective. To evaluate the combined effect of systemic corticosteroid and antibiotic therapy on the course of septic arthritis.Methods. The murine model of hematogenously acquired Staphylococcus aureus arthritis was used. Mice were treated with corticosteroids and antibiotics, and were followed up individually. Arthritis was evaluated clinically and histopathologically. Serum samples and bacterial isolates were also analyzed.Results. The prevalence of arthritis 14 days after the onset of the disease was 22% in the corticosteroid and antibiotic-treated group, as compared with 81% in the control (nontreated) group and 48% in the antibiotictreated group. The severity of arthritis also decreased in the corticosteroid and antibiotic-treated group, as did the mortality rate. Immunohistochemical analysis revealed a dramatic decrease in T cells and macrophages in the synovium of mice that took the combined therapy. The mechanisms leading to this outcome include the inhibitory effect of corticosteroids on T cell and B cell proliferation and differentiation, such as suppression of interferon-y (IFNy) production. Serum levels of IFN y were decreased 4-fold in the antibiotic-treated group compared with the controls; a 15-fold decrease was observed in the corticosteroid and antibiotic-treated animals. In addition, serum NO,-was significantly decreased in mice treated with antibiotics ( p 5 0.05), as

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SUMMARYThe aim of the study was to assess the role of the complement system in Staphylococcus aureus arthritis and septicaemia. The murine model of haematogenously acquired septic arthritis was used, injecting intravenously toxic shock syndrome toxin-1 (TSST-1), producing S. aureus LS-1. Complement was depleted using cobra venom factor (CVF). Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of complement depletion on the phagocytic activity of leucocytes was assessed in vivo and in vitro. Six days after inoculation of S. aureus the prevalence of arthritis in decomplemented mice was three-fold higher than that in controls (91% versus 25%). The clinical severity of arthritis at the end of the experiment, expressed as arthritic index, was 7·3 and 1·9, respectively. These findings were confirmed by histological index of synovitis as well as of cartilage and/or bone destruction being significantly higher in decomplemented mice than in controls (9·8 Ϯ 1·7 versus 4·9 Ϯ 1·2, P < 0·05; and 7·9 Ϯ 1·7 versus 3·0 Ϯ 0·9, P < 0·05, respectively). Also, the septicaemiainduced mortality was clearly higher in decomplemented mice compared with the controls. CVF treatment significantly reduced in vivo polymorphonuclear cell-dependent inflammation induced by subcutaneous injection of olive oil and mirroring the capacity of polymorphonuclear cells (PMNC) to migrate and/or extravasate. Besides, the decomplementation procedure significantly impaired phagocytic activity of peripheral blood leucocytes in vitro, since the number of phagocytes being able to ingest bacteria decreased by 50% when the cells were maintained in decomplemented serum compared with those in intact serum. The conclusion is that complement depletion aggravates the clinical course of S. aureus arthritis and septicaemia, possibly by a combination of decreased migration/extravasation of PMNC and an impairment of phagocytosis.