Significance of interleukin-10 and interleukin-12 levels in breast cancer patients and their possible role in tumour immunology

Rao, Vittal Sree Rama

Medicine
November 2006

Thesis or dissertation


Rights
© 2006 Vittal Sree Rama Rao. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

Patients with cancer are thought to have significant impairment of the immune system. One of the manifestations is believed to be skewing of the cytokine profile in favour of the immunosuppressive Th2 cytokine family as opposed to the immunofacilitatory Th1 cytokine family. In this MD thesis, a prospective study was undertaken to determine whether this occurred in breast cancer patients.

IL-IO (representing the Th2 cytokine family) and IL-12 (representing the Th1 cytokine family) levels in the serum, IL-12 production capability of peripheral blood mononuclear cells (PBMC) along with the levels of IL-to and IL-12 in the tumour microenvironment as detected by immunohistochemistry were determined in breast cancer patients and compared with levels in healthy volunteers. No difference in serum IL-to and IL-12 levels or IL-12 production capability of PBMC was noted between breast cancer patients and controls. Among the known prognostic factors (tumour size, grade, lymph node involvement and oestrogen receptor status), grade was found to be inversely related to serum IL-12 levels (by univariate and multivariate analysis; P=O.045). No significant association between these prognostic factors and IL-IO levels were noted. Immunohistochemistry revealed mild to intense staining for IL-IO in the tumour vicinity, but in the case of IL-12, the staining was inconclusive. The effect of therapy on the levels of IL-IO and IL-12 was also investigated. Following surgical excision, serum IL-IO levels and IL-12 production capability of PBMC did not show significant change. However, serum IL-12 levels were significantly elevated after surgery raising the possibility of a partial skewing of the immune response in favour of the Th1 cytokine profile (Wilcoxon signed ranks test, P=O.OOl). After completion of adjuvant therapy (chemotherapy and/or radiotherapy), serum IL-IO levels again did not show any significant change, but serum IL-12 levels showed a downward trend which may be due to the immunosuppressive effect of the adjuvant therapy (Wilcoxon signed ranks test, P=O.06).

In conclusion, this study did not find any evidence of Th2 bias as a manifestation of immune suppression in breast cancer patients. The change in serum IL-12 levels following surgery and adjuvant therapy is interesting and may reflect a change in immune status following the therapeutic interventions. The significance of this must be elucidated by studies with long term follow-up before definite conclusions can be made.

Publisher
Postgraduate Medical Institute, The University of Hull
Ethos identifier
uk.bl.ethos.442238
Qualification level
Doctoral
Qualification name
MD
Language
English
Extent
7 MB
Identifier
hull:16056
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