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Title: Interleukin 1 and factors that affect its activities in vivo
Author: Eastgate, Julie Ann
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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Interleukin 1 alpha and beta are well-characterised cytokines that are thought to function in localised inflammation and immunoregulation. In vitro and in vivo studies on the biological activities of IL-1 also indicate a role in the tissue destruction of many inflammatory disease processes. The detection of IL-1 in biological fluids is complicated by the presence of inhibitory and cytotoxic factors that interfere in bioassays. We have used immunoassays to measure IL-1 alpha and beta levels in human plasma. Detection of plasma IL-1 beta required a chloroform extraction step to remove factors that mask immunoreactive epitopes. We have used these procedures to compare the levels of circulating IL-1 activity in normal individuals and patients with rheumatoid arthritis (RA). RA patients had raised plasma IL-1 beta concentrations that correlated with measures of disease activity. Individuals tested longitudinally also showed correlations between disease activity and plasma IL-1 beta. Interleukin-1 alpha levels however were not raised in RA when compared to age-matched controls, but serial measurements in individual patients did correlate weakly with some conventional measures of disease activity. Biochemical studies showed that both IL-1 forms were bound to high molecular weight carriers in chloroform extracted plasma. The binding did not appear to interfere with bioactivity, but the complexes were identified by immuno- and bioassay only following chloroform extraction, suggesting the presence of other masking factors in plasma. Using iodinated IL-1 a specific 43 kDa IL-1 beta binding protein was identified in plasma and synovial fluid. This protein was partially purified and characterised. The primary translation product of IL-1 beta is a 31 kDa propeptide that requires processing to a 17 kDa peptide to become biologically active. In other studies IL-1 beta propeptide processing by monocytic cell membrane preparations was demonstrated. This proteolytic event could be inhibited by some protease inhibitors and a synthetic peptide designed from the amino acid sequence of the cleavage region of IL-1 beta propeptide.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available