Interleukin-8 and CXCR1 Receptor Functional Polymorphisms and Susceptibility to Acute Pyelonephritis

Abstract

These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux.

Chemokines as Potential Markers in Pediatric Renal Diseases

“…For instance, CCL2/MCP-1 and CXCL8/IL-8 are the chemokines more commonly associated with pediatric renal diseases [7,11,12,15,16,19,20,46,47,55,58,[65][66][67][68][69][73][74][75].…”

Studies on Clinical Characteristics, Urovirulence Factor and Host Susceptibility Gene in Pediatric Acute Lobar Nephronia

“…This underlies the importance of host factors, such as mechanistic dysfunctions like vesicoureteral reflux (VUR) and genetic variations, in patient's susceptibility to the bacterial invasion and infection (Artifoni et al 2007;Lundstedt and Leijonhufvud et al 2007;Lundstedt and McCarthy et al 2007;Sivick and Mobley 2010). The inflammatory response caused by the attachment/invasion of uropathogenic E. coli into the urinary tract is determined by different molecular interactions between the bacteria and epithelial cells (Artifoni et al 2007;Sivick and Mobley 2010). The initial recognition for bacterial attachment/invasion occurs through the coordination efforts of various toll-like receptors and different Pathogen-Associated Molecular Patterns (PAMPs) such as bacterial flagellin and lipopolysaccharide .…”

“…Following that, potent chemoattractants secreted by the infected epithelial cells will attract inflammatory cells, and the chemokine receptors will then direct recruited inflammatory cells' interactions with mucosal barrier. Subsequent steps in the inflammatory process will determine the balance between the health and the disease severity (Godaly et al 2001;Artifoni et al 2007). Neutrophil-dependent innate host defense system is considered to be an important antimicrobial process to maintain the sterility of the urinary tract.…”

“…IL-8, interleukin-8; and CXCR1, CXCR2; receptors for interleukin-8) among the pediatric UTI patients with different clinical severity; namely, acute pyelonephritis (APN) and the clinically more severe UTI disease, acute lobar nephronia (ALN) (Cheng et al, 2011a). In addition, since VUR is a well-known risk factor for severe parenchymal infectious disease as APN (Orellana et al 2004;Artifoni et al 2007), a subgroup of APN and ALN patients without VUR will also be examined to exclude the possible effects caused by VUR. Statistical analyses using log-additive model has revealed that only IL-8 (rs4073) showed significant difference in genotype frequency between the control group and APN, ALN or combined cases (Table 7.1) for APN vs. control; ALN vs. control and combined vs. control, respectively).…”

“…The allele frequency analyses have shown that the minor allele, "A", in IL-8 (rs4073) is more prevalent in the severe upper UTI groups than in the control for APN vs. control; ALN vs. control and combined vs. control, respectively (Table 7.2) (Cheng et al 2011a). Since vesicoureteral reflux (VUR) has been suggested as the significant host risk factor for upper UTIs (Orellana et al 2004;Artifoni et al 2007) (Cheng et al 2011a) has indicated that APN and ALN patients have distinctive higher AA genotype frequency and A allele occurrence in IL-8 (rs 4073) as compared to the controls. In contrast, no differences in TLR-4 (rs10759932), CXCR1 (rs16858808) and CXCR2 (rs4674258) were noted among the APN, ALN and control.…”