AB072. SOH24AB_211. Inflammatory cytokine production by human dermal fibroblasts is suppressed by 1,4,5-oxathiazinane-4,4-dioxide (OTD)
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AB072. SOH24AB_211. Inflammatory cytokine production by human dermal fibroblasts is suppressed by 1,4,5-oxathiazinane-4,4-dioxide (OTD)

Stephanie O’Callaghan, Cathriona Foley, Henry Redmond

Department of Surgery, School of Medicine, College of Medicine and Health, University College Cork, Wilton, Cork, Ireland


Background: Postoperative recurrence rates in solid cancers remain high at 20–66% even with curative resection. Prolonged surgically-induced inflammation can trigger an immunosuppressive cascade supportive of tumour progression and recurrence. By preventing excessive inflammation, immunosuppression is reduced. Potential cytokine targets include proinflammatory interleukin (IL)-6 and IL-8, produced by fibroblasts following tissue damage. This study evaluates the effect of 1,4,5-oxathiazinane-4,4-dioxide (OTD) on IL-6 and IL-8 production in human dermal fibroblasts (HDFs).

Methods: HDFs (n=3) were treated with five concentrations of OTD (0.25, 0.5, 0.75, 1 and 1.25 mM) in triplicate with or without IL-1α for 24 h. IL-6 and IL-8 levels were then quantified by electroluminescence using a V-FLEX custom panel (MesoScale Discovery). Results were statistically analysed using analysis of variance (ANOVA) with GraphPad Prism software.

Results: OTD treatment of HDFs demonstrated a dose-dependent reduction in IL-6 and IL-8 production by HDFs. IL-1α stimulation significantly increased IL-6 (P<0.05) and IL-8 (P=0.0001) production by HDFs relative to unstimulated controls. Addition of OTD to IL-1α stimulated groups significantly decreased IL-8 production at OTD concentrations of 0.5 mM (P<0.005), 0.75 mM (P=0.0001), 1 mM (P<0.0001) and 1.25 mM (P=0.0001). A significant decrease in IL-6 was observed at OTD concentration of 1 mM (P<0.05) and 1.25 mM (P<0.05). These values are expressed relative to IL-1α stimulated controls.

Conclusions: OTD suppresses the production of the pro-inflammatory cytokines IL-6 and IL-8 by HDFs. Therefore, postoperative use of OTD may be an approach to treat prolonged surgically-induced inflammation to reduce the proinflammatory IL-6 and IL-8 cytokines produced by fibroblasts following tissue damage.

Keywords: Fibroblasts; inflammation; oxathiazinane dioxide; surgical adjuvants; cytokines


Acknowledgments

Funding: None.


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


doi: 10.21037/map-24-ab072
Cite this abstract as: O’Callaghan S, Foley C, Redmond H. AB072. SOH24AB_211. Inflammatory cytokine production by human dermal fibroblasts is suppressed by 1,4,5-oxathiazinane-4,4-dioxide (OTD). Mesentery Peritoneum 2024;8:AB072.

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