In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could be detected in cytoplasmic extracts of collagenase-expressing synovial fibroblast-like cells when compared to equivalent RNA amounts isolated from control fibroblasts. Utilizing immunocytochemistry, immunoreactivity for c-fos oncoprotein was found in 13 of 19 joint specimens obtained from patients with active RA. These oncoprotein data were positively correlated to the collagenase expression in the same specimens. Moreover, immunohistochemical analysis confirmed the localization of both oncoprotein c-fos and fibroblast-type collagenase within synovial fibroblast-like cells attached to bone erosions.

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Methods. Competitive reverse transcriptasepolymerase chain reaction (RT-PCR) and enzymelinked immunosorbent assay were used to assess IFN␥ and IL-4 expression in T cell clones (TCC), T cell lines (TCL), and polyclonal CD4؉ and CD8؉ cells derived from NBS, BAL, and PB.Results. Patients with WG and chronic rhinitis were found to share in situ production of messenger RNA (mRNA) specific for IFN␥ (Th1). Only 2 patients with WG expressed IL-4, whereas IL-4 mRNA PCR products were found in inflamed tissues of the disease control patients. The granuloma-derived T cells of WG patients produced only IFN␥, while TCC, TCL, and CD4؉ and CD8؉ T cells from BAL and PB produced mainly IFN␥.Conclusion. Our data indicate that a Th1 cytokine pattern predominates in the granulomatous inflammation in patients with WG.

Objective To investigate cytokine production patterns of T cell lines (TCL) from patients with Churg‐Strauss syndrome (CSS). Methods Short‐term polyclonal TCL were generated from peripheral blood of patients with CSS or Wegener's granulomatosis (WG) and healthy controls (HC). TCL were established in the presence of interleukin‐2 (IL‐2) and phytohemagglutinin and were phenotypically characterized by flow cytometry. Th1/Th2 cytokine production by stimulated TCL (72 hours) was analyzed by enzyme‐linked immunosorbent assay. Results TCL that represented the progeny of in vivo–activated T cells from CSS patients displayed a heterogeneous immunophenotype, with a predominance of CD4+ T cells when compared with WG TCL, which were predominantly CD8+. All CSS TCL shared the ability to produce large amounts of interferon‐γ (IFNγ), IL‐4, and IL‐13 compared with HC (P = 0.014 for all 3). Production of IL‐4 and IL‐13 was higher in CSS TCL than in WG TCL (P = 0.014 for both). IL‐5 production was up‐regulated in WG TCL compared with CSS TCL (P = 0.014). Compared with HC, WG TCL showed increased production of IFNγ (P = 0.021), IL‐5 (P = 0.043), and IL‐13 (P = 0.021). Conclusion Our results indicate that, while there is evidence for both a type 1 and a type 2 response in CSS, type 2 cytokine production pattern appears to predominate in this disease when compared with WG and HC.