TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.

The susceptibility to urinary tract infection (UTI) is controlled by the innate immune response and Toll like receptors (TLRs) are the sentinels of this response. If productive, TLR4 signalling may initiate the symptomatic disease process. In the absence of TLR4 signalling the infected host instead develops an asymptomatic carrier state. The activation of mucosal TLR4 is also influenced by the properties of the infecting strain, and pathogens use their virulence factors to trigger 'pathogen-specific' TLR4 responses in the urinary tract but do not respond to the asymptomatic carrier strains in patients with asymptomatic bacteriuria (ABU). The TLR4 dependence has been demonstrated in mice and the relevance of low TLR4 function for protection for human disease was recently confirmed in children with asymptomatic bacteriuria, who expressed less TLR4 than age matched controls. Functional chemokines and functional chemokine receptors are crucial for neutrophil recruitment, and for the neutrophil dependent bacterial clearance. Interleukin (IL)-8 receptor deficient mice develop acute septic infections and chronic tissue damage, due to aberrant neutrophil function. This mechanism is relevant for human UTI as pyelonephritis prone children express low levels of the human CXCL8 (Il-8) receptor, CXC chemokine receptor 1 (CXCR1) and often have heterozygous CXCR1 polymorphisms. This review illustrates how intimately the innate response and the susceptibility to UTI are linked and sophisticated recognition mechanisms that rely on microbial virulence and on host TLR4 and CXCR1 signalling.

[Hepatocellular carcinoma in Iceland.].

INTRODUCTION: The incidence of hepatocellular carcinoma (HCC) varies throughout the world, being relatively low in Northern Europe (less than five per 100,000 population) where the majority of the patients have cirrhosis. In Iceland the prevalence of viral hepatitis and cirrhosis, the main risk factors for HCC, is lower than reported in many other countries. The aim of our study was to investigate the incidence and etiology of HCC in Iceland. MATERIAL AND METHODS: All patients diagnosed with HCC in Iceland in 1984-1998 were included in the study. Histologic diagnosis was required for inclusion. Patients were identified from the Icelandic Cancer Registry and by reviewing autopsy and histopathology reports. Further information was obtained from medical records. RESULTS: A total of 71 cases of HCC were identified, 51 males and 20 females. The mean age for males was 69.3 years (18-95) and 73 years (52-89) for females. The age-standardized annual incidence rate of HCC was 1.08/100,000 (males 2.10, females 0.67). The incidence did not increase significantly during the study period. Alcohol abuse (15.5%) and hemochromatosis (11%) were the most common risk factors. Twenty-three (32%) had cirrhosis but 39 (55%) had no known risk factors. Of 55 cases where non-neoplastic tissue was available for examination, 27 had liver disease. CONCLUSIONS: 1) The incidence of HCC in Iceland is lower than reported in other countries. 2) Alcohol abuse and hemochromatosis are the most common risk factors. 3) The ratio of patients with cirrhosis is low.