Barkley, Diana Elizabeth Helen; (1990) Cell-associated interleukin 1 in rheumatoid arthritis. Doctoral thesis (M.D), UCL (University College London).

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Abstract

This thesis outlines the development of a specific method for identifying cell-associated IL-1α and IL-1β at the single cell level and the application of this method in normals and patients with RA. The findings are summarised below: 1. In normal peripheral blood mononuclear cells (PBM) activated with mitogen in vitro distinct populations of cells produce the two subtypes IL-1α and IL-1β. 2. Significantly more cell-associated IL-1α is seen in the unactivated blood of patients with RA compared to normals and controls. The percentage of bright IL-1α staining cells correlates with CRP. No IL-1β staining is seen. 3. Significantly fewer IL-1α staining cells are seen in the blood of RA patients receiving parenteral gold therapy. 4. Incubation of normal PBM with GM-CSF reproduces the picture of staining seen in RA blood. This is markedly inhibited by gold in vitro. The above findings have not been reported before. The method developed allows the study of the two IL-1 subtypes at the single cell level and may be useful in the future to study IL-1 production by different cell types in health and disease. The results in normal blood may be important in understanding the reason for the existence of two forms of IL-1 with identical biological activities. Cell-associated IL-1α has not been previously reported in RA blood and may play an important role in the disease pathogenesis. GM-CSF may be involved in the induction of cell-associated IL-1α in vivo in RA and gold may exert its therapeutic effect via inhibition of this IL-1α production. The findings in RA blood may be important in understanding the role of IL-1α in this disease and suggest possible sites of action for novel therapeutic agents.

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