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Background: It has been suggested that the immunopathology of rheumatoid nodules parallels that of inflamed synovium in rheumatoid arthritis (RA)., Objective: To analyse the effect of infliximab on the immunopathology of rheumatoid nodules in order to provide new insights into the relationship between synovial inflammation and rheumatoid nodules., Materials and Methods: Nodules were present at baseline in six patients with RA and after infliximab treatment in five patients, including paired nodules before and after treatment in three patients. In one patient, the nodule appeared during treatment. Paraffin sections were used for histological analysis. Frozen sections were stained by immunohistochemistry for cellular markers (CD3, CD4, CD8, CD16, CD20, CD68), blood vessels (CD146, vWF, alphavbeta3), and adhesion molecules (E-selectin, VCAM-1, ICAM-1)., Results: No manifest immunopathological differences were found between the nodules before and after infliximab treatment. All nodules depicted the classical structure with a central necrotic zone, surrounding the palisade layer, and an outer connective tissue zone. Immunohistochemistry showed the presence of CD68+ and CD16+ macrophages in the palisade and the connective tissue zone, as well as a small number of CD3+, CD4+ T lymphocytes in the perivascular areas. Small vessels were seen in the connective tissue and were sometimes positive for the neovascularisation marker alphavbeta3. They expressed no VCAM-1, E-selectin weakly, but ICAM-1 strongly. ICAM-1 was also strongly expressed on palisade cells., Conclusions: Despite an improvement of articular symptoms, infliximab treatment had no distinct effect on the histopathology of rheumatoid nodules, suggesting that different pathogenetic mechanisms mediate the two disease manifestations in RA.

Mycophenolate mofetil (MMF) is a new immunosuppressive agent currently used in organ transplantation and under evaluation in immune-mediated inflammatory disorders such as rheumatoid arthritis. Although MMF was shown to inhibit purine nucleotide synthesis in lymphocytes, it is still unclear whether it might also exert direct antiinflammatory actions in vivo. To address this question, we evaluated the effects of MMF administration on the responses of mice to a single challenge with bacterial lipopolysaccharide (LPS). We observed that MMF treatment inhibits the release of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) upon LPS injection whereas it promotes IL-10 production. In parallel, MMF was found to protect mice from LPS-induced lethality. Inhibition of TNF-alpha release was also observed in IL-10-deficient mice indicating that it does not exclusively depend on the upregulation of IL-10 endogenous synthesis. In view of the differential effects of MMF on the LPS-induced production of TNF-alpha and NO on one hand and that of IL-10 on the other hand, we conclude that beside its immunosuppressive action at the lymphocyte level, MMF is also endowed with antiinflammatory properties.

We investigated the effects of methotrexate (MTX) on the production of tumor necrosis factor (TNF), nitric oxide (NO) and interleukin-10 (IL-10) in vivo. Administration of low doses of MTX (450 mug/kg once a week for 4 weeks) in Balb/c mice resulted in a significant inhibition of the systemic release of TNF and NO upon LPS challenge, whereas the production of IL-10 remained unchanged. These anti-inflammatory effects of MTX were exerted at the macrophage level since peritoneal macrophages from mice, injected for 4 weeks with MTX produced lower levels of TNF than cells from control mice upon LPS stimulation ex vivo. In parallel, we found that MTX-treated mice were less susceptible to a lethal challenge with LPS and D-galactosamine. MTX did not inhibit TNF release after injection of Concanavalin A (ConA) or anti-CD3 monoclonal antibody (mAb), indicating that MTX does not inhibit TNF production at the T cell level. We conclude that repeated administration of a low dose of MTX in mice is associated with a decreased production of TNF by macrophages upon LPS activation.

Two cases of primary biliary cirrhosis with bone lesions are reported. In one case radiographic findings in the hands and right shoulder are found to be characteristic of primary biliary cirrhosis rather than other concomitant diseases present in the patient which are also susceptible to produce bone lesions. The second case is an example of less specific bone changes which may be attributed to primary biliary cirrhosis or other rheumatoid disease.

A commercial serologic test using purified antigens of Helicobacter pylori has been evaluated in the diagnosis of this infection. In a series of 250 patients undergoing endoscopy with antral biopsies for cytology, histology and culture, serology was positive in 68 of 71 patients with a positive culture (sensitivity: 96%) and negative in 67 of 69 patients with a normal mucosa and no microorganisms on biopsy (specificity: 97%). In the entire series, serology was positive in 33 patients with no infection on biopsies (13%). In a group of 205 blood donors, we confirmed an increasing prevalence with age, ranging from 13% in subjects less than 30 years old to 38% in subjects more than 60 years old.