Correlations between the Intrarenal Expression of Various Cytokines and Chemokines and the Clinicopathologic Characteristics in IgA Nephropathy / 대한신장학회잡지

ABSTRACT

IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults, and the pathogenetic mechanisms seem to be diverse. Proinflammatory cytokines, Th1/Th2 cytokines, and chemokines would be involved in the pathogenetic pathways and would affect the functional and histologic consequences. To evaluate this hypothesis, we tried to quantify the magnitude of intrarenal gene expression of various cytokines(TNF-alpha, IL-1beta, IL- 6, IL-15, IFN-gamma, IL-2, IL-10) and chemokines(IL-8, RANTES) in 61 renal core biopsy specimens confirmed as IgA nephropathy by immunofluorescent microscopy. Semiquantitative reverse-transcriptase polymerase chain reactions(RT-PCR) using the internal competitors were done for the quantification of gene transcripts. And using the immunohistochemistry (IHC), we tried to determine the degree of expression and the location of various cytokines and chemokines in renal tissues in 29 patients among the above patients. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than that in patients with normal renal function(p=0.0483). Gene transcript levels of proinflammatory cytokines(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(p=0.0363). IL-10 gene transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of TNF-alpha(p=0.0026), IL-10(p=0.0092) and IFN-gamma(p=0.0188) were related to the degree of mesangial matrix expansion, and the extent of intrarenal arteriolar lesions correlated with the expression of the IL-8 genetranscript(r=0.3828, p=0.0033). The cellular infiltration in glomeruli was related with chemokine(IL-8) gene expression, but the relation was not significant statistically. The degree of IgA deposition in glomeruli was related with the expression of IL-6 and IL-15. The expression of intrarenal gene transcripts of various cytokines and chemokines were closely interrelated. Th1 or Th2 cytokine polarization was not present in IgA nephropathy. In IHC, TNF-alpha, IFN-gamma and IL-2 were immunostained dominantly in mesangial region, but not in tubulointerstitial region. In contrast, positive reactions for IL-10 were observed mainly in tubules. The significant reactions for IL-8 were noted in the periarteriolar and arteriolar areas. The results of RT- PCR and IHC showed positive relationships, but those were not significant statistically. This study suggests that proinflammatory, Th1/ Th2 cytokines and chemokines are involved in the specific processes of inflammation and immunologic injury, and their predominance and the level of expression could determine the pathogenetic processes and the severity of the clinical manifestations in IgA nephropathy.