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Title: Antibacterial host defence mechanisms in rheumatoid arthritis
Author: Frame, Margaret W.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1989
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The present in vitro studies employed a radioassay, incorporating tritiated [3H] thymidine, to measure phagocytic uptake of Staphylococcus aureus (S. aureus) by polymorphonuclear leucocytes (PMNs) of patients with rheumatoid arthritis (RA) and healthy controls. An intrinsic defect was detected in the phagocytic capacity of peripheral blood (PB) PMNs from patients with RA. Serum from RA patients and normals had a similar inhibitory effect on PMN phagocytosis. However, synovial fluid (SF) from RA patients was found to impair phagocytic ability by acting directly on the PMN. Furthermore, these SF significantly impaired PMN uptake as compared to SF from patients with various other arthritides. No correlation was found between defective phagocytosis and age, disease activity, drug therapy, the amount of circulating immune complexes (ICs) or rheumatoid factor (RF). Also, the lack of correlation between clinical parameters such as titres of RF and complement components, suggests factors other than ICs may be involved in this inhibitory activity. Complement levels and heat-labile opsonic activity were lower in SF from RA patients than SF from other forms of arthritis or normal serum. Nevertheless, none of the RA sera or SF tested lacked opsonic activity. Interleukin 1 (IL-1) production by monocytes of RA patients and normal subjects were studied both spontaneously and after lipopolysaccharide (LPS) and S. aureus stimulation. Interleukin 1 activity was measured using the LBRM TG-6/HT2 bioassay system. Rheumatoid arthritis monocytes spontaneously produced more IL-1 than the controls and this difference was maintained after stimulation. When paired PB and SF monocytes were compared, SF cells produced less IL-1 than corresponding PB monocytes, but more than normal PB monocytes. This was similarly observed after stimulation. These findings suggest that this line of host defence is not impaired in RA patients. However, a high concentration of IL-1 may be detrimental to the PMNs migrating into the SF from the PB. Hydrocortisone sodium phosphate was found to inhibit IL-1 production. This is not true for the other anti-rheumatic drugs studied. Thus, the findings of these studies suggest that the increased incidence of bacterial infection in RA patients is the consequence of impaired PMN phagocytosis. The mechanism underlying this defect could be intrinsic to the cell, and amplified by extracellular inhibitory factors present in SF, as yet to be characterised.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available