TUMOR-NECROSIS-FACTOR SOLUBLE RECEPTOR-I AND RECEPTOR-II AND INTERLEUKIN-1 RECEPTOR ANTAGONIST IN ACUTE PYELONEPHRITIS IN RELATION TO BACTERIAL VIRULENCE-ASSOCIATED TRAITS AND RENAL-FUNCTION

Urinary tract infections activate both mucosal and systemic inflammato ry responses reflected by elevation of cytokine concentrations in seru m and urine, We determined urine and serum concentrations of tumour ne crosis factor soluble receptors I and II (sTNFR I and sTNFR II) and in terleukin-l receptor antagonist (IL-1ra) in 41 women with acute pyelon ephritis caused by Escherichia coli, 2 weeks after the infection, duri ng a subsequent episode of cystitis or asymptomatic bacteriuria and al so later when the same patients were free from bacteriuria. Concentrat ions of sTNFR I, sTNFR II and IL-1ra were related to the expression of five virulence markers of E. coli, glomerular filtration rate (GFR) a nd to the concentration of C-reactive protein (CRP) in serum. Patients with acute pyelonephritis had elevated serum concentrations of sTNFR I and sTNFR II compared to healthy women (P<0.001 for both comparisons ). The concentrations of sTNFR I and sTNFR II in urine were significan tly higher in patients with acute pyelonephritis compared to controls (P<0.001 in both cases). The concentration of sTNFR II in urine was hi gher in patients infected by E. coli producing haemolysin (P=0.05) and in patients infected by E. coli expressing hydrophobic properties (P= 0.05) compared to patients infected by strains without these virulence traits. Patients who had high concentrations of sTNFR II in serum dur ing acute pyelonephritis had lower GFR at follow-up (r=-0.48, P=0.05). Patients who responded with a marked increase in CRP had higher sTNFR I and sTNFR II in urine (r=0.58, P<0.01 and r=0.48, P<0.01, respectiv ely), The concentrations of sTNFR I and sTNFR II in serum and urine de creased during follow-up and were lower 2 weeks after the infection wh en all patients were free from bacteriuria. IL-1ra in serum was elevat ed during pyelonephritis (P<0.001) while that in urine was significant ly lower compared to controls (P<0.001). It is concluded that the incr eased concentrations of TNF receptors may block the cytotoxic and infl ammatory actions and reduce the sensibility of renal cells to TNF alph a-mediated effects.