Clinical Microbiology
Annelie Brauner
Research Group

RESEARCH PROJECTS

Acute pyelonephritis, APN, is an important bacterial infection in early childhood. In some children, APN leads to renal scarring and permanent kidney damage which is a major cause of chronic renal failure, that later may require dialysis. In patients with continuous ambulatory peritoneal dialysis, CAPD, peritonitis is the most common complication. Infections induce an inflammatory response in which the cytokine network plays a major role. Knowledge of the cytokine response in the kidney and dialysate is necessary for better understanding of the mechanisms behind as well as the relative importance of different bacterial characteristics for the local inflammatory reponse and postinfectious renal scarring. The possibility to modulate the cytokine response may influence the progress of the disease. The aims are to study cytokine production in body fluids and intracellularly; to correlate the results to renal scarring, infecting microorganisms and host factors; to modulate the cytokine response pharmacologically.

 

1) Cytokine production: In patients with infections (APN and CAPD peritonitis) cytokine levels and soluble cytokine receptors are studied in urine, dialysate and serum. Cells of importance are analysed using immunohistochemistry and in situ hybridization. The results are correlated to the infecting microorganism and bacterial virulence factors as well as clinical and renal data. 2) Experimental APN: E. coli is used to induce APN in mice, and the development and progress of renal scarring is studied histopathologically and cytokine production is analysed using immunohistochemistry and in situ hybridization. 3) Immunomodulation: Cytokine response is modulated with steroids and pentoxifyllin in experimental APN.

 

Research results:

1) Acute pyelonephritis: Presence of persistent uptake defects on DMSA scintigraphy, probably reflecting renal scarring were only seen in children with an increased IL-6 ratio in the acute phase while increased IL-1a levels were associated with less renal inflammation and scarring.
2) CAPD: Elevated levels of inflammatory cytokines were found in dialysate in the acute stage of patients with peritonitis, and were highest in infections with high virulent strains.
3) Experimental APN: After bladder inoculation of mice, P-fimbriae negative E. coli strain elicited lower IL-6 levels that persisted for a longer time, than the isogenic P-fimbriae positive strain.

Selected references:

1. Brauner A, Carlsson B, Sundkvist G, Östenson C-G. False positive treponemal serology in patients with diabetes mellitus. J Diab Compl 1994;8:57-62.
   
2. Brauner A, Kaijser B, Kühn I. Recurrent Escherichia coli bacteremia - clinical characteristics and bacterial properties. J Infect 1994; 28:49-57.
   
3. Tullus K, Fituri O, Burman LG, Wretlind B, Brauner A. Interleukin-6 and interleukin-8 in the urine of children with acute pyelonephritis. Pediatric Nephrol 1994; 8:280-284.
   Jacobson SH, Hylander B, Wretlind B, Brauner A. Interleukin-6 and interleukin-in serum and urine in patients with acute pyelonephritis in relation to bacterial virulence associated traits and renal function. Nephron 1994; 67: 172-179.

   Tullus K, Noack G W, Burman L G, Nilsson R, Wretlind B, Brauner A. Elevated cytokine levels in tracheobronchial aspirate fluids from ventilator treated neonates with bronchopulmonary dysplasi. In press J Pediatr.

   Gottfarb P, Brauner A. Children with persistent cough-outcome with treatment and role of Moraxella catarrhalis? Scand J Infect Dis 1994;26:545-551.

   Brauner A, Katouli M, Östenson C-G. P-fimbriation and hemolysin production are important virulence factors in diabetic patients with E. coli bacteremia. A multivariate statistical analysis of seven bacterial virulence factors. In press J Infect.

   Tullus K, Fituri O, Linné T, Escobar-Billling R, Karlsson A, Burman LG, Wretlind B, Brauner A. Urine interleukin-6 and interleukin-8 in children with acuite pyelonephritis, in relation to DMSA scintigraphy in acute phase and at 1-year follow-up. Pediatr Radiol 1994; 24:513-515.