Excessive expression of the tumor necrosis factor-alpha gene in the kidneys of patients with membranous glomerulonephritis.
BACKGROUND
The implication of cytokines in the pathogenesis of membranous glomerulonephritis (MGN) and minimal change disease (MCD) is not well known. To delineate the pathogenic roles of cytokines in MGN and MCD, renal tissue from patients with a variety of glomerulonephritides was studied for cytokine mRNA expression.


METHODS
The renal tissue from patients with MGN, MCD, focal segmental glomerulosclerosis, acute tubulointerstitial nephritis, diabetic nephropathy, immunoglobulin (Ig) A nephropathy, hypertensive nephrosclerosis, IgM nephropathy, amyloidosis and glomerulosclerosis were studied for the expression of cytokines (tumor necrosis factor, [TNF]-alpha, interleukin [IL]-1 beta, IL-2, IL-4, IL-8 and IL-10) by reverse transcriptase polymerase chain reaction.


RESULTS
The frequency for renal expression of TNF-alpha was significantly higher in patients with MGN than in patients with other diseases (p = 0.0295, as analyzed by Fisher's exact test). Its expression in MCD was also more frequent than in the controls, although not significant (p = 0.0794). IL-4 transcript was demonstrated in cultured lymphocytes stimulated with or without pokeweed mitogen in two patients with MCD.


CONCLUSIONS
TNF-alpha, which is mainly produced by macrophages and neutrophils, is excessively expressed in the kidneys of patients with active MGN and MCD. IL-4, on the other hand, is expressed in the lymphocytes of patients with MCD. These results suggest that TNF-alpha and IL-4 may be involved directly or indirectly in the pathogenesis of these two diseases.
Wu
T H
TH
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, ROC.
Tsai
C Y
CY
Yang
W C
WC
D002478:Cells, Cultured; D015433:Glomerulonephritis, Membranous / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics; D007668:Kidney / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4