The levels of IL-6 and soluble IL-33R are increased in the renal vein during surgery for clear cell renal cell carcinoma. (August 2021)

• Record Type: Journal Article
• Authors: Gudbrandsdottir, Gigja; Aarstad, Helene H.; Hjelle, Karin M.; Førde, Kristina; Reisæter, Lars; Bostad, Leif; Aarstad, Hans J.; Beisland, Christian
• Is Part Of: Cytokine. Volume 144(2021)
• Publication Date: 2021-08
• Subjects: IL-6 -- soluble IL-33R -- Gp130 -- Clear cell renal cell carcinoma -- Surgery; ASA American Society of Anesthesiologist -- BS Blood sample -- CHRCC Chromophobe Renal Cell Carcinoma -- CC Clear cell -- CE Contrast enhancement -- DSS Disease specific survival -- ECOG-PS Eastern Cooperative Oncology Group-Performance Status -- ISUP International Society of Urological Pathology -- IHC Immunohistochemistry -- MDT Multidisciplinary Team -- PRCC Papillary Renal Cell Carcinoma -- ROI Region of Interest -- RCC Renal Cell Carcinoma -- RV Renal Vein; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2021.155586
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Serum levels of IL-6 is increased during surgery for renal cell cancer. Intraoperative IL-6 values are higher in the renal vein compared to peripherally. Intraoperative IL-33R values are higher in the renal vein compared to peripherally. Other IL-6 and IL-1 cytokines and receptors show overall stability. There is a high expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature. Abstract: Purpose: The main aim was to map serum levels of IL-1/IL-6 family cytokines and relevant receptors from serum samples taken across treatment in patients with Renal Cell Carcinoma (RCC). Additionally, we explored the possible interactions between these measurements, immunohistochemistry and intratumoral blood flow. Methods: We included 40 patients undergoing open surgery for renal tumors. Blood samples were collected before, during (taken simultaneously from a peripheral site and the renal vein (RV) before clamping) and after surgery. Samples were analyzed for IL-6, IL-27, IL-31, OSM, TNF-α, serum (s)-gp130, s-IL-6Rα, s-IL-33R, IL-1Rα and VEGF. All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. Immunohistochemistry for the CCRCC group included expression of IL-6/IL-6R. Intratumoral blood flow was determined by calculating intratumoral contrast enhancement on preoperative computerized tomography (CT) imaging. Results: In the CCRCC patients, the intraoperative RV concentration of IL-6 was significantly higher than in both the preoperative and postoperative samples (p = 0.005 and p = 0.032, respectively). Furthermore, the intraoperative ratio showed significantly higher levels of IL-6 in the RV than in the simultaneously drawn peripheral sample. Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. Increased blood flow in the CCRCC tumors predicted increased IL-6 levels in the RV (p < 0.001). The other cytokines and receptors showed an overall stability across the measurements. However, the intraoperative ratios of IL-33R and gp130 showed significantly higher levels in the RV. Conclusion: Serum levels of IL-6 increased during surgery. Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. Other studied cytokines/receptors were remarkably stable across all measurements.