Studies on Interleukin-6: Its Role in the Acute Phase Response and Its Clinical Value as a Marker of Tissue Damage

Cruickshank, Anne McDonald (1992) Studies on Interleukin-6: Its Role in the Acute Phase Response and Its Clinical Value as a Marker of Tissue Damage. MD thesis, University of Glasgow.

Abstract

In vitro evidence suggests that interleukin-6 (IL-6) is a major mediator of the acute phase response. The aims of this work were threefold: firstly, to validate a bioassay for the measurement of IL-6 in serum; secondly, to characterise the role of IL-6 in the acute phase response and determine its potential as a marker of tissue damage using elective surgical patients as models of controlled trauma; and thirdly, to assess its value in four clinical situations : post-operative complications; suspected myocardial infarction; pancreatitis; and rheumatoid arthritis. The validation of a hybridoma growth stimulation assay using the mouse 7TD1 cell line with colorimetric evaluation of cell numbers is described. This assay was used to measure serum IL-6 concentrations at timed intervals post-operation in 39 patients from 6 broad surgical categories. Serum IL-6 rose within 2 to 4 hours of incision in all surgical groups. The magnitude of the IL-6 response was strongly associated with duration of surgery, and was associated significantly with C-reactive protein (CRP) response, increase in axillary temperature and reduction in zinc/albumin ratio. Surgical patients who subsequently developed complications had higher IL-6 concentrations 24 hours post-operation than those who did not. Serum IL-6 was also measured in 15 patients with suspected myocardial infarction, in 23 patients with acute pancreatitis, and in 33 patients with rheumatoid arthritis. In patients with suspected myocardial infarction, admission serum IL-6 concentration discriminated completely between those with angina and those who had suffered myocardial infarction, and was strongly associated with left ventricular ejection fraction on the third hospital day. Patients who had severe pancreatitis had higher serum IL-6 levels on admission than those with mild disease. Serum IL-6 concentrations in rheumatoid arthritis were significantly associated with clinical disease activity. These results are consistent with the hypothesis that IL-6 is a major mediator of the systemic inflammatory response, and indicate that it behaves as an early, quantitative marker of tissue damage. Its measurement is likely to be of value in clinical practice, particularly in acute situations, but larger numbers of patients require to be studied to confirm these findings.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Alan Shenkin
• Keywords: Medicine, Biochemistry
• Date of Award: 1992
• Depositing User: Enlighten Team
• Unique ID: glathesis:1992-74541
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Sep 2019 17:51
• Last Modified: 27 Sep 2019 17:51
• URI: https://theses.gla.ac.uk/id/eprint/74541