Cytokines in fluids from polycystic kidneys

Abstract

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 (less than 20 to 419 pg/ml, TNF alpha in 54 of 75 (less than 10 to 73 pg/ml), stromelysin in 18 of 23 (less than 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.

Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease

“…Chemokines and cytokines were found at high concentrations in cyst fluid and produced by cyst-lining epithelial cells (169). Recently, alternatively activated macrophages aligned along cyst walls were detected in polycystic kidneys from conditional Pkd1 knockout and the Pkd2 WS25/-model (170,171).…”

Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease

“…Chemokines and cytokines were found at high concentrations in cyst fluids and were found to be produced by cyst-lining epithelial cells. 115 More recently, many alternatively activated macrophages aligned along cyst walls have been detected in polycystic kidneys from conditional Pkd1-knockout and Pkd2 WS25/2 mice. 116,117 Macrophage depletion by intraperitoneal liposomal clodronate administration inhibits epithelial cell proliferation and cyst growth and improves renal function.…”

Macrophages Promote Cyst Growth in Polycystic Kidney Disease

“…For example, proinflammatory cytokines such as IL-1␤, TNF-alpha (TNF-␣), and IL-2 are found in cyst fluid samples from human kidneys. 5 Zheng et al reported the presence of monocyte chemoattractant protein-1 (MCP1) in urine of ADPKD patients, 7 and, more recently, Grantham and colleagues demonstrated that high levels of urinary MCP-1 strongly correlate with the rate of subsequent cyst growth. 8 Consistent with this, Cowley et al reported increased expression of Mcp1, accompanied by accumulation of ED-1 positive macrophages, in the kidneys of Han:SPRD polycystic rats, a nonorthologous model of ADPKD.…”