PubMed Health⌕ Search

Biomedical subjects

S Hedges

Publications and source records attributed to S Hedges.

26 records · Page 2Linked to original sources
PubMed1993

Bacterial adherence and epithelial cell cytokine production.

Epithelial cell lines produce the cytokines IL-1 alpha, IL-6 and IL-8 when stimulated with Escherichia coli. The cytokine response is enhanced by P fimbriae. The epithelial cell lines also respond to stimulation with other cytokines. These in vitro findings were confirmed in vivo in patients with E. coli infection who secreted IL-6 and IL-8 into the urine. The observations suggest that epithelial cells play a more active role in the mucosal immune response than previously recognized.

Animals↗
PubMed1992

Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria.

The mucosal and systemic interleukin-6 (IL-6) response to urinary tract infection was analyzed in women with acute pyelonephritis or asymptomatic bacteriuria. Urine and serum samples were obtained at diagnosis and after treatment. IL-6 activity was elevated in urine samples from most bacteriuric women, regardless of the severity of infection. Urinary levels greater than 20 units/mL occurred in 25 of 29 women with acute pyelonephritis and in 36 of 42 women with asymptomatic bacteriuria. Elevated serum IL-6 levels were found mainly in patients with acute pyelonephritis: Levels greater than 20 units/mL occurred in 14 of 28 women with acute pyelonephritis compared with 0 of 28 women with asymptomatic bacteriuria. These results suggest that bacteriuria is accompanied by elevated urinary IL-6 levels and that this IL-6 is locally produced. The spread of IL-6 to the circulation in patients with acute pyelonephritis may contribute to the elevation of fever and C-reactive protein characteristic of the disease.

Adult↗
PubMed1992

Lps genotype in the C57 black mouse background and its influence on the interleukin-6 response to E. coli urinary tract infection.

The present study examined the influence of the mouse Lps genotype on the interleukin-6 (IL-6) and polymorphonuclear leucocyte (PMN) responses to mucosal Escherichia coli infection. Lipopolysaccharide (LPS) responder C57BL/6J (Lpsn, Lpsn) and LPS non-responder C57BL/10ScCr (Lpsd, Lpsd) mice were inoculated intravesically with Escherichia coli Hu734. The secretion of IL-6, the recruitment of PMNs into urine, and the bacterial clearance from the kidneys and bladders were compared between the two mouse strains at 2, 6 and 24 h after infection. The C57BL/6J mice showed a high PMN response and rapid clearance of bacteria from the kidneys and bladders. In the C57BL/10ScCr mice the PMN response was low and infection remained. This supported a role of the Lps genotype in these events. The IL-6 levels remained low after infection in both LPS responder and non-responder mice, but became elevated in the animals which were accidentally traumatized during infection. The IL-6 response to trauma alone was independent of Lps genotype, but the response to trauma and infection combined differed between the mouse strains. The IL-6 response to trauma and infection was more rapid in the C57BL/6J than in the C57B1/10ScCr mice. The traumatized and infected animals did not clear the infection as efficiently as the non-injured animals in both backgrounds. The difference in PMN recruitment and susceptibility of infection between LPS responder and non-responder mice in the C57 Black background followed the pattern previously seen in the C3H mouse background and suggested that these events were under Lps gene control. An effect of the Lps locus on the IL-6 response could be detected only in traumatized and infected animals.

Animals↗
PubMed1992

Interleukin-6 response of epithelial cell lines to bacterial stimulation in vitro.

This study demonstrated that epithelial cell lines secrete interleukin-6 (IL-6) in response to stimulation with gram-negative bacteria. Human epithelial cell lines of urinary tract origin (A-498 and J82) and of intestinal origin (HT-29 and Caco-2) were analyzed for the secretion of IL-6 by using the B9 bioassay. The supernatants from cells maintained with culture medium were used to assess the constitutive production of IL-6. The supernatants from cells exposed to Escherichia coli strains, lipopolysaccharide, lipid A, and isolated fimbriae were used to quantitate the IL-6 response to these stimulants. The urinary tract epithelial cell lines were found to constitutively secrete IL-6. The IL-6 activity in the supernatants of the bladder cell line (J82) increased above constitutive levels after 2 h of stimulation by most of the bacterial strains tested. The IL-6 activity in the supernatants of the kidney line (A-498) accumulated at a constant rate over the 24-h assay period. The role of bacterial adherence for the induction of IL-6 production was investigated by comparing the responses to recombinant E. coli strains expressing different fimbriae. In addition, isolated P and S fimbriae with and without the receptor binding domain were also used as stimulants. The IL-6 activity in the supernatants of the bladder cell line increased after exposure to bacteria and bacterial products regardless of their adhesive properties. In contrast, the kidney cell line was stimulated to secrete significantly more IL-6 by adhering bacteria and by adhesin-positive P fimbriae than by nonadhering bacteria or adhesin-negative P fimbriae. The S-fimbrial preparations had no specific effects on the IL-6 activity of the cell supernatants. These results are consistent with our hypothesis that epithelial cells can be a major source of IL-6 when stimulated by bacteria and that the adhesive properties of the bacteria can influence this response.

Bacterial Adhesion↗
PubMed1991

Interleukin-6 response to deliberate colonization of the human urinary tract with gram-negative bacteria.

Intravesical inoculation of patients with Escherichia coli provided an opportunity to examine the interleukin-6 (IL-6) response to a gram-negative bacterial urinary tract infection in humans. All patients secreted IL-6 as a result of infection. Urinary IL-6 was not continuously secreted but appeared as a series of similar peaks during the first 48 h after infection. There was no significant difference in the ability to trigger IL-6 secretion between isogenic adhering or nonadhering strains, but a threshold concentration of 10(5) bacteria per ml of urine was necessary to fully stimulate IL-6 secretion. There was no detectable increase in IL-6 levels in the serum of the colonized individuals, suggesting mainly local IL-6 production. These results demonstrate that IL-6 is a part of the human mucosal response to gram-negative urinary tract infections.

Adult↗
PubMed1990

Ciclosporin-dependent, nu-independent, mucosal interleukin 6 response to gram-negative bacteria.

Regulation of the mucosal inflammatory response to Gram-negative bacteria was analysed. The interleukin 6 (IL-6) secretion, influx of polymorphonuclear leucocytes into urine, and bacterial clearance from the kidneys were compared between Balb/c (nu/nu) and nu/+/- mice, with and without ciclosporin (CsA) treatment. There was no significant influence of the nu genotype on any of the host responses measured. CsA pretreatment significantly decreased Il-6 secretion in both nu/nu and nu/+/- mice, but did not affect bacterial clearance or the leucocyte response in any mouse strain tested. Tissue damage, in addition to bacterial infection, resulted in significantly higher levels of IL-6 than bacterial infection alone. Tissue-damaged mice were significantly less likely to clear the bacterial infection than their non-damaged counterparts, but there was no significant difference in the leucocyte response. CsA pretreatment did not significantly reduce the levels of IL-6 in the tissue-damaged mice. These results demonstrate that the mucosal inflammatory response to Gram-negative infection, including IL-6 secretion, is nu-independent, and that bacterial infection alone or in combination with tissue damage induce IL-6 secretion by two different pathways.

Animals↗