Inflammatory infiltrate and interleukin-8 expression in the synovium of psoriatic arthritis – an immunohistochemical and mRNA analysis

Abstract

Psoriatic arthritis is an inflammatory arthropathy that ultimately can lead to joint destruction. In this study, we investigated the immunophenotype of the inflammatory cells and the expression of interleukin-8 (IL-8), which is the hallmark chemoattractant cytokine of psoriasis in synovial membranes from patients exhibiting active psoriatic synovitis (n=9). The tissue samples were examined by immunohistochemistry, Western blot analysis and in situ hybridisation. The inflammatory infiltrate consisted predominantly of CD3⁺ T lymphocytes, with a higher proportion of CD4⁺ than CD8⁺ T lymphocytes in six cases. CD3⁺ T lymphocytes were focally distributed near small blood vessels and the enlarged synovial intima. CD1⁺ interdigitating reticulum cells were not detected. CD22⁺ B lymphocytes and plasma cells were found in small aggregates without KiM4⁺ follicular dendritic cells. KiM8⁺ macrophages were located in the synovial intima and were distributed in a diffuse pattern near the synovial lining cells. CD15⁺ neutrophil granulocytes were detected in four cases. They were preferentially located in the vicinity of blood vessels and the synovial intima. IL-8 was found at a high level in the synovial lining cells and to a lesser extent in cells located in the perivascular areas. Immunofluorescence double staining showed IL-8 to be expressed in KiM8⁺ multinucleated giant cells, KiM8⁺ macrophages and CD3⁺ T lymphocytes. IL-8 receptor A was demonstrated in the synovial lining and in macrophages and lymphocytes. IL-8 was detected by immunoblot analysis of the synovial tissue at 8.4 kD. Employing in situ hybridisation, IL-8 mRNA was strongly and preferentially expressed in the synovial intima, as well as in macrophages and lymphocytes. The immunophenotype of the psoriatic arthritis inflammatory cells shows great similarity to the inflammatory infiltrate found in the synovial tissue of patients with rheumatoid arthritis. The preferential expression of IL-8 and IL-8 mRNA in the enlarged synovial intima and in lymphocytes and macrophages suggests that IL-8 exerts its action through activated mononuclear cells and T lymphocytes. It seems to play a role in regulating leucocyte traffic into the enlarged synovial intima and may contribute to the aggressive synovitis of patients with psoriatic arthritis.