A New IL-6-Inducing Mechanism in Cancer with New Therapeutic Possibilities
(2024) In Cancers 16(21).- Abstract
Background: Interleukin-6 is dysregulated in multiple pathological conditions, e.g., cancer and inflammatory diseases. Aim: To investigate new mechanisms for the regulation of pathological IL-6 production. Methods: PBMCs (peripheral blood mononuclear cells) stimulated by cancer serum factors or specific peptides produce interleukin-6 (IL-6). Immunoregulatory albumin neo-structures and peptides were identified with 2D gel electrophoresis and MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) analyses. Il-6 and albumin neo-structures were determined by ELISA (enzyme-linked immunosorbent assay). Results: Conformational changes in normal serum albumin by proteolytic degradation generates an... (More)
Background: Interleukin-6 is dysregulated in multiple pathological conditions, e.g., cancer and inflammatory diseases. Aim: To investigate new mechanisms for the regulation of pathological IL-6 production. Methods: PBMCs (peripheral blood mononuclear cells) stimulated by cancer serum factors or specific peptides produce interleukin-6 (IL-6). Immunoregulatory albumin neo-structures and peptides were identified with 2D gel electrophoresis and MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) analyses. Il-6 and albumin neo-structures were determined by ELISA (enzyme-linked immunosorbent assay). Results: Conformational changes in normal serum albumin by proteolytic degradation generates an IL-6-inducing neo-structure, IL-6-inducing factor (IL-6IF). This neo-structure is immunogenic which results in the production of autoantibodies. IL-6 production induced by IL-6IF and cancer patient sera is inhibited by specific antibodies. The serum concentration of IL-6IF is significantly higher in advanced cancer stages, and its presence is significantly correlated with the survival of the patients. Conclusions: A new mechanism for the induction IL-6 synthesis is presented. Based on this mechanism, the pathological IL-6 production related to enhanced proteolytic activity can be diagnosed and selectively inhibited by specific antibodies. Such antibodies were identified and purified. Thus, the neo-structure, inducing pathological IL-6 production, associated with a reduced survival of cancer patients, can be selectively removed by the therapeutic administration of antibodies leaving the function of IL-6 needed for the normal activity of the immune system intact.
(Less)
- author
- Håkansson, Leif LU ; Dunér, Pontus LU ; Broströmer, Erik LU ; Gustavsson, Bengt ; Wettergren, Yvonne ; Ghafouri, Bijar ; Håkansson, Annika LU and Clinchy, Birgitta
- organization
- publishing date
- 2024-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- albumin neo-structure, autoantibodies, cancer, IL-6-inducing factor, immune complexes, immunoregulation, interleukin-6, PBMCs, prognosis
- in
- Cancers
- volume
- 16
- issue
- 21
- article number
- 3588
- publisher
- MDPI AG
- external identifiers
-
- scopus:85208386838
- pmid:39518029
- ISSN
- 2072-6694
- DOI
- 10.3390/cancers16213588
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2024 by the authors.
- id
- bda55d86-c97f-441b-abac-311f073ef353
- date added to LUP
- 2025-01-14 14:02:06
- date last changed
- 2025-07-16 04:59:17
@article{bda55d86-c97f-441b-abac-311f073ef353,
abstract = {{<p>Background: Interleukin-6 is dysregulated in multiple pathological conditions, e.g., cancer and inflammatory diseases. Aim: To investigate new mechanisms for the regulation of pathological IL-6 production. Methods: PBMCs (peripheral blood mononuclear cells) stimulated by cancer serum factors or specific peptides produce interleukin-6 (IL-6). Immunoregulatory albumin neo-structures and peptides were identified with 2D gel electrophoresis and MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) analyses. Il-6 and albumin neo-structures were determined by ELISA (enzyme-linked immunosorbent assay). Results: Conformational changes in normal serum albumin by proteolytic degradation generates an IL-6-inducing neo-structure, IL-6-inducing factor (IL-6IF). This neo-structure is immunogenic which results in the production of autoantibodies. IL-6 production induced by IL-6IF and cancer patient sera is inhibited by specific antibodies. The serum concentration of IL-6IF is significantly higher in advanced cancer stages, and its presence is significantly correlated with the survival of the patients. Conclusions: A new mechanism for the induction IL-6 synthesis is presented. Based on this mechanism, the pathological IL-6 production related to enhanced proteolytic activity can be diagnosed and selectively inhibited by specific antibodies. Such antibodies were identified and purified. Thus, the neo-structure, inducing pathological IL-6 production, associated with a reduced survival of cancer patients, can be selectively removed by the therapeutic administration of antibodies leaving the function of IL-6 needed for the normal activity of the immune system intact.</p>}},
author = {{Håkansson, Leif and Dunér, Pontus and Broströmer, Erik and Gustavsson, Bengt and Wettergren, Yvonne and Ghafouri, Bijar and Håkansson, Annika and Clinchy, Birgitta}},
issn = {{2072-6694}},
keywords = {{albumin neo-structure; autoantibodies; cancer; IL-6-inducing factor; immune complexes; immunoregulation; interleukin-6; PBMCs; prognosis}},
language = {{eng}},
number = {{21}},
publisher = {{MDPI AG}},
series = {{Cancers}},
title = {{A New IL-6-Inducing Mechanism in Cancer with New Therapeutic Possibilities}},
url = {{http://dx.doi.org/10.3390/cancers16213588}},
doi = {{10.3390/cancers16213588}},
volume = {{16}},
year = {{2024}},
}