Clinicopathological correlation of intrarenal cytokines and chemokines in IgA nephropathy.
The pathogenetic mechanisms of IgA nephropathy are diverse and are not yet clearly elucidated. We believe pro-inflammatory cytokines, Th1/Th2, and chemokines would be involved in the pathogenetic pathways and would affect the functional and histological consequences of IgA nephropathy. By using semiquantitative reverse transcriptase-polymerase chain reactions (RT-PCR), we measured the level of intrarenal gene expression of various cytokines and chemokines in 61 renal core biopsy specimens confirmed as IgA nephropathy. And, by using immunohistochemistry (IHC), the degree of expression and the location of various cytokines and chemokines in renal tissues in 29 of the above patients were attempted to be determined. In RT-PCR, the gamma-interferon (IFN-gamma)/interleukin-10 (IL-10) ratio was higher in patients with renal dysfunction than in those with normal renal function. The levels of pro-inflammatory cytokine gene transcripts (tumor necrosis factor-alpha (TNF-alpha), IL-1beta) were high in patients with significant proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high. The level of IL-10 gene transcript was related to the severity of tubular atrophy and interstitial fibrosis. The extent of intrarenal arteriolar lesions correlated with the expression of the IL-8 gene transcript. The degree of IgA deposition in glomeruli was related to the expression of IL-15 and IL-6. In IHC, TNF-alpha, IFN-gamma and IL-2 were immunostained dominantly in the mesangial region, but not in the tubulointerstitial region. In contrast, positive reactions for IL-10 were observed primarily in tubules. Significant reactions for IL-8 were noted in the periarteriolar and arteriolar areas. The results of RT-PCR and IHC showed positive relationships, but these were not statistically significant. This study suggests that pro-inflammatory, Th1/Th2 cytokines and chemokines are involved in the specific processes of inflammation and immunological injury in IgA nephropathy.
Lim
Chun Soo
CS
Department of Internal Medicine, Seoul Municipal Boramae Hospital, Seoul, Korea. cslimjy@snu.ac.kr
Yoon
Hyung Jin
HJ
Kim
Yon Su
YS
Ahn
Curie
C
Han
Jin Suk
JS
Kim
Suhnggwon
S
Lee
Jung Sang
JS
Lee
Hyun Soon
HS
Chae
Dong-Wan
DW
D000293:Adolescent; D000328:Adult; D000368:Aged; D018925:Chemokines / Q000032:analysis / Q000096:biosynthesis*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D018925:Chemokines; D016207:Cytokines