CYTOKINES IN FLUIDS FROM POLYCYSTIC KIDNEYS

We sought evidence of cytokine presence and interleukin-1-beta (IL-1-beta) bioactivity in 104 aerobic culture negative cyst fluids (CFs) from 13 kidneys of 13 patients with symptomatic normal to end-stage autosomal dominant polycystic kidney disease (ADPKD). ELISAs were used to detect IL-1-beta, interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-alpha) and stromelysin. Prostaglandin E2 (PGE2) was detected by radioimmunoassay. IL-1-beta was present in 65 of 94 (< 20 to 419 pg/ml, TNF-alpha in 54 of 75 (< 10 to 73 pg/ml), stromelysin in 18 of 23 (< 1.0 to 56 ng/ml), IL-2 in 7 of 23 (0.1 to 1.3 ng/ml) and PGE2 in 9 of 10 fluids (0.03 to 0.49 ng/ml). Of 51 fluids with immunoreactive IL-1-beta, 36 were mitogenic for thymocytes. IL-1-beta concentrations correlated directly with those of IL-2; IL-1-beta presence was associated with higher stimulation indices, higher mean concentrations of TNF-alpha, IL-2, stromelysin, and PGE2, and with positive endotoxin assays, suggesting activation of the cytokine cascade in vivo. Cytokine, stromelysin and PGE2 concentrations did not correlate with sodium or non-sodium solute concentrations, nor with CF blood, osmolality, or endotoxin activity, indicating that differences in concentrations among fluids could not be explained by differences in water content. These data identify cytokines as candidate contributors to the morbidity and pathogenesis of ADPKD.