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.