CYTOKINE GENE-EXPRESSION DURING EXPERIMENTAL ESCHERICHIA-COLI PYELONEPHRITIS IN MICE

Purpose: We studied nine inflammatory and immunoregulatory cytokines i n acute pyelonephritis and urethral obstruction in mice to better unde rstand the processes underlying kidney inflammation and scarring. Mate rials and Methods: Experimental acute pyelonephritis was established i n Bki NMRI outbred mice by bladder inoculation of Escherichia coli, fo llowed by 6 h urethral obstruction. The numbers of cytokine mRNA expre ssing cells for interleukin-1 (IL-1), IL-4, IL-6, IL-10, IL-12, tumor necrosis factor alpha (TNF-alpha), TNF-beta, transforming growth facto r beta (TGF-beta) and interferon gamma (IFN-gamma) were determined in the kidneys and spleens from the infected, non-infected but obstructed and untouched mice using in situ hybridization with radio-labelled ol igonucleotide probes at 12 h, 48 h and 6 d after release of the urethr al obstruction. Results: Kidney cell expression of IL-1, IL-6 and TNF- alpha mRNA was observed already at 12 h and persisted on day 6 in the infected animals. A significant proinflammatory cytokine response occu rred also in the non-infected obstructed animals, albeit later and at lower levels. A marked increase of IL-4, IL-10, TGF-beta and IFN-gamma mRNA producing cells was also found in the kidneys of these two group s again with higher levels in the infected animals. Very high numbers of splenocytes expressing mRNA for IL-1 were observed especially in th e infected animals. A high proportion of splenocytes further expressed mRNA for IL-6, TNF-alpha, IL-4, IL-10, IFN-gamma and TGF-beta, again with highest numbers in the infected group of animals. Conclusions: Th e present study extends previous knowledge about the local and systemi c cytokine expression profiles during acute pyelonephritis and after u rethral obstruction. Of particular interest was the marked kidney cell expression of mRNA for TGF-beta, presumed to be important both for ob structive and post-infectious renal scarring.