Biomedical subjects

M Kunaver

Publications and source records attributed to M Kunaver.

3 recordsLinked to original sources

PubMed1999

Cytokine production by synovial T cells in rheumatoid arthritis.

OBJECTIVE: To investigate the production of cytokines by T cells in patients with rheumatoid arthritis (RA), reactive arthritis (REA) and osteoarthritis (OA). METHODS: The lymphokines interleukin (IL)-2, IL-4, interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta), as well as the monokines IL-1, IL-6 and TNF-alpha, were measured by immunoassays in sera and synovial fluid (SF) from patients with RA, REA and OA. In addition, cytokine expression was studied by immunohistochemistry in synovial membrane tissue sections from patients with RA and OA. RESULTS: Almost 60% of RA sera contained at least one of the cytokines investigated, though in low concentrations, whereas cytokines were generally not detectable in sera from REA and OA patients. In contrast, cytokines were found in virtually all SF; thus, the majority of SF from RA patients contained IFN-gamma (median level 17 pg/ml) in addition to the monokines IL-6 (4700 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not TNF-alpha) were also frequently measured in SF from REA patients, whereas OA samples typically contained only IL-6. Immunohistochemical analysis of tissue sections from RA patients revealed lymphokine expression in 0.1-0.3% of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also IL-4. Interestingly, the expression of TNF-alpha and IL-6 by synovial T cells was also observed. The majority of cytokine-expressing T cells were CD4-positive T-helper cells typically found in perivascular areas, whereas cytokine-producing CD8-positive T cells were found distributed throughout the synovium. As expected, in specimens from OA patients, T cells were much less abundant and expression of cytokines could not be detected. CONCLUSION: These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.

Adolescent↗

PubMed1996

The role of T-lymphocytes and cytokines in rheumatoid arthritis.

In this review the involvement of T cells, in addition to that of the monocyte/macrophage lineage, in the pathogenesis of rheumatoid arthritis is discussed. The evidence for the pathogenetic importance of T cells is based upon their state of activation in the synovial membrane and the cytokines produced. These cytokines can be detected in synovial fluids as well as in the synovial membrane by both immunohistochemistry and in situ hybridization. However, cytokine production can be detected only in a minor fraction of the T cells which contrasts the number of non-T cells observed to synthesize cytokines. Nevertheless, it can be assumed that the small amount of lymphokines is sufficient to activate a cytokine cascade derived from other cells. The cytokine profile secreted is indicative for a T cell response that primarily involves Th1-like cells.

Animals↗

PubMed1993

Intercellular adhesion molecules in normal synovium.

The vasculature of normal synovium and skin has been examined for the presence of molecules believed to be involved in intercellular adhesion and whose expression on endothelial cells in vitro is known to be upregulated by cytokines. Synovium was obtained from clinically and histologically normal joints removed during amputations for proximal sarcomata. Skin was obtained from healthy volunteers. Cryostat sections of tissues were assessed by immunohistochemistry and microdensitometry for the presence of E-selectin using monoclonal antibody 1.2B6, intercellular adhesion molecule-1 (ICAM-1) using monoclonal antibody 6.5B5 and vascular cell adhesion molecule (VCAM-1) using monoclonal antibody 1.4C3. Both E-selectin and ICAM-1 were present on a proportion of normal synovial venules but at a level comparable to or lower than that found on dermal vessels. (Staining intensities given as mean absorption indices: superficial synovium 1.2B6: 9.9 +/- 11.4, 6.5B5: 10.2 +/- 12.0, deep synovium 1.2B6: 6.6 +/- 9.9, 6.5B5: 24.6 +/- 15.7, skin 1.2B6: 13.1 +/- 16.6, 6.5B5: 36.4 +/- 12.9.) E-selectin expression was most prominent on small superficial venules in synovium and ICAM-1 most strongly expressed on larger, deep venules. VCAM-1 was found at low levels on cells associated with vessel walls but no significant endothelial staining was seen in either type of tissue. VCAM-1 was also present on cells of the synovial lining layer. Some of the findings in synovium could have been attributable to tumour related cytokine release, but the consistency of findings and comparability to skin suggest that this is relatively unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗