Bench-to-bedside review: Ventilation-induced renal injury through systemic mediator release - just theory or a causal relationship?

Kuiper, Jan Willem; Vaschetto, Rosanna; Corte, Francesco Della; Plötz, Frans B; Groeneveld, AB Johan

doi:10.1186/cc10282

Critical Care

Table 3 Potential effects on the kidney of mediators released during mechanical ventilation

From: Bench-to-bedside review: Ventilation-induced renal injury through systemic mediator release - just theory or a causal relationship?

Mediator	Effects on kidney	References
Pro-inflammatory
TNF-α	Stimulated expression of TGF-β, RANTES, MIP-2, MCP-2, IL-1β, TNF-α, T-cell activation 3, IL-6, phospholipase-A2, LIF. MHC-I upregulation	[37–40, 43]
	Leukocyte infiltration through MCSF, MCP-1, GRO-α, β, γ, ENA-78, GCP-2, IL-8, MIP-1β and 3α, RANTES, ICAM-1, VCAM-1, L-selectin	[44–49]
	Death receptor- and mitochondrial-mediated apoptosis and ceramide signaling. Necrosis through ROS. Downregulation of anti-apoptotic proteins.	[50–54, 56–59]
	Production of vasoactive mediators: PAF, ET-1, PGs, adenosine, NO. Downregulation Ang-II-R	[60–69, 72]
	NO tubular epithelial cell shedding. Decreased proliferation of tubular and mesangial cells	[73, 74]
	Increased PAI-1 gene expression, increased TF production with fibrin deposition	[75, 76]
	Decreased gene expression for urea, glucose, sodium and chloride transporters/channels	[77–80]
	Decreased gene expression of nuclear hormone receptor LXR, its target genes and coactivators	[81]
IL-1β	Stimulated expression of IL-6, IL-8, LIF, ceramide. MHC-I upregulation	[40, 43, 87–89]
	Increased expression of MCP-1, GMCSF, MSF, ENA-78, RANTES, MIP-1β, ICAM-1	[90–93]
	Downregulation of Ang-II-R. Expression of NO, PGE2	[39, 72, 94, 95]
	Stimulated growth of glomerular epithelial cells	[96]
	Increased TF expression and activity, upregulation of tPA and PAI-1	[97, 98]
	Decreased gene expression for urea, glucose, sodium and chloride transporters/channels	[77–80]
	Decreased gene expression of nuclear hormone receptor LXR, its target genes and coactivators	[81]
IL-6	TNF-α, IL-1β stimulation. Increased ICAM-1, P-selectin expression with neutrophil infiltration	[105–107]
	Increased survival, upregulation of pro- and anti-apoptotic genes	[108]
	Decreased expression of Ang-II-R	[72]
	Increased oxidative stress, but increased expression of HO-1, Ref-1	[105, 106]
	Proliferation of rat mesangial and tubular cells, increased HGF and met-c receptor. Conflicting reports	[109–111]
	Decreased gene expression for urea, glucose and chloride transporters	[77–79]
	Abrogation of protective effect of hyperlipidemia	[115]
Anti-inflammatory
IL-10	Decreased synthesis of TNF-α and IL-1β	[118, 119]
	Contradictory effects on ICAM-1 expression and leukocyte infiltration	[118, 120]
	Prevention of apoptosis and necrosis. Decreased cell cycle activity	[118]
	Reduction of VEGF, iNOS and nitrite formation	[118, 121]
	Proliferation of mesangial cells	[122–124]
sTNFR	Decreased expression of TNF-α, MCP-1	[71]
	Inhibition of apoptosis, decreased cell proliferation and fibrosis	[128–130]
IL-1RA	Decreased gelatinase B, stromelysin, MCP-1 and IL-8	[132, 133]
	Decreased ICAM-1 expression and leukocyte infiltration	[134–138]
Chemotactic
IL-8	Increased COX1 and PGE2 expression	[145]
	Alterations in glomerular basement membrane sulfate metabolism	[146]
MIP-2	Increased MCP-1, RANTES, MIP-2	[151]
	Decreased neutrophil influx	[152, 153]
	Decreased fibrin deposition	[152]
KC = GRO-α	Increased MCP-1, RANTES, MIP-2, KC	[151]
	Neutrophil infiltration	[153]
	Stimulated proliferation of medullary collecting duct cells	[154]
	Increased COX1 and PGE2 synthesis	[145]
MCP-1	Increased IL-6	[155]
	Increased ICAM-1 expression, chemotaxis and haptotaxis, monocyte/macrophage infiltration	[155–165]
	Increased apoptosis	[164]
	Increased fibrosis, TGF-β, collagen deposits	[165–167]
	Decreased nephrin	[168]
Coagulation/fibrinolysis
Active PAI-1	Increased leukocyte infiltration	[169]
	Fibrin, collagen deposits, increased fibronectin, TGF-β, decreased urokinase and fibrosis	[169–172]
tPA	Conflicting reports on leukocyte infiltration	[175, 178]
	Conflicting reports on fibrosis	[175–178]
aPC	Decreased TNF-α, IL-6, IL-8, IL-18	[180–182]
	Decreased KC, MIP-2, MCP-1, suppression of leukocyte rolling, adhesion and infiltration	[180–184]
	Decreased apoptosis, necrosis	[180–185]
	Decreased nitrosative stress	[185]
	Decreased adrenomedullin, iNOS, angiotensin (II), ACE. Increased renal and peritubular blood flow, decreased permeability	[180, 181, 184]
	Decreased extracellular matrix depositions	[180, 185]
Miscellaneous
VEGF	Decreased MCP-1, ICAM-1, leukocyte infiltration	[188]
	Decreased apoptosis and necrosis	[189–192]
	Stimulated eNOS and NO expression	[193, 194]
	Increased permeability	[195, 196]
	Increased proliferation of glomerular cells, podocytes, mesangial cells, fibroblasts and capillaries	[192, 194, 213–220]
	Conflicting reports of fibrosis and sclerosis	[194, 217, 219–221]
	Sustained nephrin expression	[221]
sFasL	Increased apoptosis	[10]

ACE, angiotensin converting enzyme; Ang-II-R, angiotensin-II receptor; aPC, activated protein C; COX, cyclooxygenase; ENA, epithelial neutrophil activating protein; eNOS, endothelial nitric oxide synthase; ET, endothelin; GCP, granulocyte chemotactic peptide; GMCSF, granulocyte macrophage colony-stimulating factor; GRO, growth related oncogene; HGF, hepatocyte growth factor; HO, heme-oxygenase; ICAM, intercellular adhesion molecule; IL-1RA, interleukin-1 receptor antagonist; iNOS, inducible nitric oxide; KC, keratinocyte-derived chemokine; LIF, leukemia inhibitory factor; LXR, liver X receptor/retinoid X receptor; MCP, monocyte chemoattractant protein; MCSF, macrophage colony stimulating factor; MHC, major histocompatibility complex; MIP, macrophage inflammatory protein; MSF, migration stimulating factor; NO, nitric oxide; PAF, platelet activating factor; PAI, plasminogen activator inhibitor; PG, prostaglandin; RANTES, regulated upon activation, normal T-cell expressed, and secreted; Ref, restriction factor; ROS, reactive oxygen species; sFasL, soluble Fas ligand; sTNFR, soluble TNF-α receptor; TF, tissue factor; TGF, transforming growth factor; tPA, tissue type plasminogen activator; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor.

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ISSN: 1364-8535

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