Colonic explant lactate concentration and inflammatory protein secretion in ulcerative colitis
C McShane, F O’Connell, R Corcoron, P MacDonagh, J O’Sullivan, D Kevans
1. Department of Gastroenterology, St James's Hospital, Dublin 8 2. Trinity Translational Medicine Institute, Trinity College Dublin 3. Department of Surgery, Trinity College Dublin, St James’s Hospital, Dublin 8
Lactate, the end product of glycolysis, exerts both pro and anti-inflammatory effects depending on the cell type and metabolic microenvironment.
We aimed to investigate if lactate concentration in tissue cultured media (TCM) from ulcerative colitis (UC) patient-derived explants is associated with TCM concentration of inflammatory proteins known to be involved in UC pathogenesis.
UC patients were prospectively recruited. Endoscopic biopsies were collected from the sigmoid colon and TCM generated as per previously described methods. Patients demographics, baseline characteristics and disease behaviour were characterised. TCM secreted lactate was quantified using a colorimetric L-Lactate assay (Abcam, UK). Secreted inflammatory protein profiles were analysed via 54 V-plex ELISA (Meso Scale Diagnostics, USA).
21 patients were recruited (age [mean, range] 50.48, 20-72years; 52% female; disease duration [mean, range] 9.81, 0-29years). 38% were receiving biologic therapy. Median lactate concentration:154.4 (IQR 98.57-206) nmol/μg of protein. Baseline explant TCM lactate did not correlate with TCM CRP r=0.16 (95%CI -0.29 – 0.55), p=0.49. TCM lactate was directly correlated with pro-inflammatory protein secretion: IL-23 r=0.79 (95%CI 0.54 – 0.91) p<0.001, TNF-a r=0.90 (95%CI 0.77– 0.96), p<0.001 and VEGF r=0.91 (95%CI 0.78– 0.96), p<0.001. Lactate was directly correlated with the secretion of immunoregulatory cytokine IL-10 r=0.74 (95%CI 0.46 – 0.89) p<0.001.
Lactate plays a key role in immunometabolism, acting as a metabolic mediator. Lactate concentration is correlated with the concentrations of important inflammatory proteins involved in IBD pathogenesis. Further studies are needed to elucidate the complex functional effects of lactate on the IBD microenvironment.