O104 Effect of a surgical adjuvant on IL-6 and IL-10 levels produced by human dermal fibroblasts using an in vitro wound healing model

Abstract

Abstract Introduction Interleukin-6 (IL-6) and Interleukin-10 (IL-10) are members of the cytokine family demonstrating pro-inflammatory and anti-inflammatory properties respectively. Disruption in the balance of inflammation postoperatively leads to wound complications and cancer recurrence. Surgical adjuvants including 1,4,5-oxathiazinane-4,4-dioxide (OTD) can reduce inflammation while also demonstrating cytotoxic effects on cancer cells. Thus, we evaluated the effect of OTD on Human Dermal Fibroblasts (HDFs) and subsequent IL-6 and IL-10 levels. Methods Five concentrations of OTD were applied to HDF cells over time to assess migration and wound closure. Leica Las X software and a light microscope were used to obtain photographs at nine timepoints. After 30 hours cell media was removed and levels of IL-6 and IL-10 were measured. Migration and wound closure were assessed using percentage area of the wound gap, determined using ImageJ. Results OTD application demonstrated a dose-dependent arrest in fibroblast migration, greatest at 3-6 hours. This is represented by greater percentage area relative to control (15%Area – 6hrs) for concentrations 0.75mM (19%Area – 6hrs), 1mM (25%Area – 6hrs) and 1.25mM (30.5%Area - 6hrs). Percentage area was greater for 1mM and 1.25mM at 3hrs relative to 0hrs indicating gap widening, however for 0.75mM %Area was reduced. This correlated with IL-6 and IL-10 levels which were raised at 30hrs for 1mM and 1.25mM but not 0.75mM. Conclusion Lower concentrations of OTD do not demonstrate a negative effect on fibroblast migration, IL-6 and IL-10 levels despite previously demonstrated cytotoxic effects on cancer cells. Thus, OTD is a potential surgical adjuvant in cancer treatment.