Cytokines in glomerulonephritis.
Cytokines play central roles in both innate and adaptive immune responses that lead to renal inflammation. They are involved systemically in cross-talk between antigen-presenting cells, leukocytes, and regulatory cells to initiate and modulate nephritogenic immunity. Within the kidney, cytokines play a central role in signaling between infiltrating leukocytes and intrinsic renal cells and orchestrate the effector responses that lead to renal damage. Glomerulonephritis (GN) is an important cause of renal inflammation leading to renal failure that results from adaptive responses targeted at the kidney. Animal models of GN have shown that cytokines play critical roles in initiation and modulation of renal inflammatory responses through their ability to modulate the T helper 1/T helper 2 balance of nephritogenic immune responses. Evidence from clinical studies is now confirming the importance of this paradigm in directing the inflammatory mechanisms, histologic patterns, and clinical consequences of human GN. Cytokines also have critical intrarenal effector roles in the development, perpetuation, and resolution of GN. The proinflammatory role of intrarenal cytokine production by leukocytes in GN is well recognized, but, more recently, the role of intrinsic renal cell cytokine production in amplifying renal inflammation has been shown in animal models of GN. Studies showing benefits of specific anticytokine therapies directed at tumor necrosis factor in human GN are now appearing.
Tipping
Peter G
PG
Centre for Inflammatory Diseases, Department of Medicine, Monash Institute for Medical Research, Monash University, Clayton, Victoria, Australia. peter.tipping@med.monash.edu.au
Holdsworth
Stephen R
SR
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D006801:Humans
D016207:Cytokines