Protection with Antibody to Tumor Necrosis Factor Differs with Similarly Lethal Escherichia coli  versus Staphylococcus aureus  Pneumonia in Rats

2003 ◽  
Vol 99 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Waheedullah Karzai ◽  
Xizhong Cui ◽  
Bjoern Mehlhorn ◽  
Eberhard Straube ◽  
Thomas Hartung ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Tumor Necrosis Factor ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Lung Lavage ◽  
Arterial Oxygen ◽  
E Coli ◽  
Oxygen Gradients ◽  
Necrosis Factor

Background Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia. Methods Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h. Results Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P > or = 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6; P = 0.006) and S. aureus (-0.5 +/- 0.04; P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P < or = 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003). Conclusion Antibody to TNF improved host defense and survival rates with both lethal E. coli and S. aureus pneumonia, but protection was greater with E. coli, where TNF concentrations were higher than with S. aureus. The efficacy of antiinflammatory agents in sepsis may be altered by bacteria type.

scholarly journals Trace amounts of antibiotic exacerbated diarrhea and systemic inflammation of weaned pigs infected with a pathogenic Escherichia coli

2021 ◽  
Vol 99 (3) ◽  
Author(s):  
Kwangwook Kim ◽  
Yijie He ◽  
Cynthia Jinno ◽  
Lauren Kovanda ◽  
Xunde Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Tumor Necrosis Factor ◽  
Blood Cell ◽  
Tumor Necrosis ◽  
Basal Diet ◽  
Weaned Pigs ◽  
Ileal Mucosa ◽  
E Coli ◽  
Mesenteric Lymph ◽  
Necrosis Factor

Abstract The experiment was conducted to investigate the effects of trace amounts of antibiotic on growth performance, diarrhea, systemic immunity, and intestinal health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli. Weaned pigs (n = 34, 6.88 ± 1.03 kg body weight [BW]) were individually housed in disease containment rooms and randomly allotted to one of the three dietary treatments: nursery basal diet (CON) and two additional diets supplemented with 0.5 or 50 mg/kg carbadox to the nursery basal diet (TRA or REC), respectively. The experiment lasted 18 d with 7 d before and 11 d after the first E. coli inoculation. The E. coli F18 inoculum was orally provided to all pigs with a dose of 1010 colony-forming unit (CFU)/3 mL for three consecutive days. Fecal and blood samples were collected on day 0 before inoculation and days 2, 5, 8, and 11 postinoculation (PI) to test the percentage of β-hemolytic coliforms in total coliforms and complete blood cell count, respectively. Sixteen pigs were euthanized on day 5 PI, whereas the remaining pigs were euthanized at the end of the experiment to collect the jejunal and ileal mucosa and mesenteric lymph node for gene expression and bacterial translocation, respectively. Pigs in REC had greater (P < 0.05) final BW and lower (P < 0.05) overall frequency of diarrhea compared with pigs in the CON and TRA groups. Pigs in TRA had the lowest (P < 0.05) average daily gain and feed efficiency from day 0 to 5 PI, highest (P < 0.05) percentage of β-hemolytic coliforms in fecal samples on days 2 and 5 PI, and greatest (P < 0.05) bacterial colonies in mesenteric lymph nodes on day 11 PI compared with pigs in the CON and REC groups. Pigs in TRA had the greatest (P < 0.05) neutrophils on day 5 PI and higher (P < 0.05) white blood cell counts and lymphocytes than other groups on day 11 PI. Pigs in TRA had the greatest (P < 0.05) serum C-reactive protein on days 2 and 5 PI and serum tumor necrosis factor-α on day 5 PI, compared with pigs in the CON and REC groups. Pigs fed REC had increased (P < 0.05) mRNA expression of zona occludens-1 (ZO-1) and occludin (OCDN) and reduced (P < 0.05) interleukin-1 beta (IL1B), interleukin-6 (IL6), and tumor necrosis factor-alpha (TNFA) in ileal mucosa on day 5 PI, compared with the CON, whereas TRA upregulated (P < 0.05) mRNA expression of IL1B, IL6, and cyclooxygenase-2 (COX2) in the ileal mucosa on day 11 PI, compared with the REC. In conclusion, trace amounts of antibiotic may exacerbate the detrimental effects of E. coli infection on pig performance by increasing diarrhea and systemic inflammation of weanling pigs.

scholarly journals Hemolytically Active (Acylated) Alpha-Hemolysin Elicits Interleukin-1β (IL-1β) but Augments the Lethality of Escherichia coli by an IL-1- and Tumor Necrosis Factor-Independent Mechanism

1998 ◽  
Vol 66 (9) ◽  
pp. 4215-4221 ◽  
Author(s):  
Thomas G. Gleason ◽  
C. Webster Houlgrave ◽  
Addison K. May ◽  
Traves D. Crabtree ◽  
Robert G. Sawyer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
E Coli ◽  
Alpha Hemolysin ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT Many pathogenic Escherichia coli produce the toxin alpha-hemolysin (Hly), and lipopolysaccharide (LPS), interleukin-1 (IL-1), and tumor necrosis factor (TNF) have all been recognized as important effector molecules during infections by gram-negative organisms. Despite the characterization of many in vitro effects of hemolysin, no direct relationship has been established between hemolysin, LPS, proinflammatory cytokine production, and E. coli-induced mortality. Previously, we have shown in vivo that hemolysin elicits a distinct IL-1α spike by 4 h into a lethal hemolytic E. coli infection. Using three transformedE. coli strains, WAF108, WAF270, and WAH540 (which produce no Hly [Hlynull], acylated Hly [Hlyactive], or nonacylated Hly [Hlyinactive], respectively), we sought to determine the specific roles of hemolysin acylation, LPS, IL-1, and TNF in mediating the lethality of E. coli infection in mice. WAF270 was 100% lethal in BALB/c, C3H/HeJ, and C57BL/6 mice; in mice pretreated with antibody to the type 1 IL-1 receptor; in type 1 IL-1 receptor-deficient mice; and in dual (type 1 IL-1 receptor-type 1 TNF receptor)-deficient mice at doses which were nonlethal (0%) with both WAF108 and WAH540. At lethal doses, WAF270 killed by 6 ± 2.3 h while WAF108 and WAH540 killed at 36 ± 9.4 and 36 ± 13.8 h, respectively. These differences in mortality were not due to IL-1 or TNF release, and the enhanced expression of LPS, which corresponded to Hly expression, was not likely the primary factor causing mortality. We demonstrate that bacterial fatty acid acylation of hemolysin is required in order for it to elicit IL-1 release by monocytes and to confer its virulence on E. coli.

scholarly journals Potency of endotoxin from bicarbonate dialysate compared with endotoxins from Escherichia coli and Shigella flexneri.

1995 ◽  
Vol 5 (8) ◽  
pp. 1634-1637
Author(s):  
L A Bland ◽  
J C Oliver ◽  
M J Arduino ◽  
C W Oettinger ◽  
S K McAllister ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Shigella Flexneri ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
E Coli ◽  
Factor Alpha ◽  
Necrosis Factor

Endotoxin is a potent activator of the complement system and other host immunoregulators, including the cytokines, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6. In this study, the potency of an endotoxin from bicarbonate dialysate was compared with endotoxins from two enteric microorganisms, Shigella flexneri and Escherichia coli. Endotoxin concentrations were standardized for the three endotoxins by use of the Limulus amebocyte lysate turbidimetric assay. Endotoxin potency was assessed by the comparative plasma concentrations of tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 after an in vitro whole-blood challenge by each type of endotoxin. Blood collected from 10 hemodialysis patients was spiked with 0.1, 1, and 10 ng/mL of E. coli and Shigella endotoxin and with 1 and 10 ng/mL of bicarbonate dialysate endotoxin. After incubation, plasma was separated and frozen at -70 degrees C until assayed for cytokine concentrations. Dialysate endotoxin was found to be 10 to 100 times less potent than E. coli and Shigella endotoxins. It was concluded that there are significant differences in the potency of endotoxins from different strains of bacteria and that these differences should be noted when designing or evaluating studies on the clinical effects of endotoxins in hemodialysis settings.

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