Modification of Human Neutrophil Response to Endotoxin with Polymyxin B Sulfate

Corrigan, James J.; Sieber, Otto F.; Ratajczak, Helen V.; Bennett, Bobbie B.

doi:10.1093/infdis/130.4.384

Cited by 33 publications

(14 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipopolysaccharide (LPS) in the experimental medium containing 200 mol/L of NEFA was below the limit of detection of LPS (5 pg/mL), indicating that LPS contamination was not a cause of increased monocyte adhesion. Experiments conducted with the addition of polymyxin B, an antibiotic that binds to the lipid A portion of LPS and inhibits LPS activity, 14 yielded similar results and confirmed this conclusion. This effect of NEFA was concentration-related, with increasing amounts of the NEFA mixture leading to increased monocyte adhesion ( Figure 1B).…”

Section: Effects Of Nefa On Monocyte Adhesionmentioning

confidence: 54%

Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells

Zhang

Schwartz

Wang

et al. 2006

ATVB

View full text Add to dashboard Cite

Objective-Monocyte proinflammatory activity has been demonstrated in obesity, insulin resistance, and type 2 diabetes, metabolic conditions that are frequently associated with elevated levels of nonesterified fatty acids (NEFA). We therefore tested the hypothesis that NEFA may induce monocyte inflammation. Methods and Results-Monocytes exposed to NEFA for 2 days demonstrated a dose-related increase in intracellular reactive oxygen species (ROS) formation and adhesion to endothelial cells. All of these effects were inhibited by the coaddition of antioxidants such as glutathione or butylated hydroxytoluene, by inhibition of ROS generation by NADPH oxidase inhibitors, and by inhibition of protein kinase C, a recognized stimulator of NAPDH oxidase.

show abstract

Section: Effects Of Nefa On Monocyte Adhesionmentioning

confidence: 54%

Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells

Zhang

Schwartz

Wang

et al. 2006

ATVB

View full text Add to dashboard Cite

show abstract

“…The second reason had to do with the time of administration of the antibiotic. It has been shown by us and other investigators that the timing of the polymyxin injection appears to be critical in order to effectively neutralize the endotoxin (3,6,7,14). In the pretreatment animals, the polymyxin was given before the establishment of an endotoxemic state and, as can be seen by the data, effectively prevented the development of endotoxin-induced leukopenia and thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

“…One human study suggested that endotoxin-induced changes Detroit, MI, lot 503545) (5). in the neutrophils could be prevented under certain circumstances White blood cell counts were performed by standard hematowith polymyxin B sulfate (6). These data strongly suggest that logic technique and platelet counts were performed by phase 48 microscopy employing the Unopette (Beckton, Dickinson and Co., Cockeysville, MD) (1).…”

Section: Summarv Polymyxin B Has Antiendotoxin Activity Which Is Distmentioning

confidence: 99%

“…Quantitative colony counts using heparinized whole blood were performed by pour plate technique on 5% blood agar plates his investigation and other reports have shown that ~o l~m~x i n (h4icro-~ech Diagnostics, Tucson, AZ). The plates were incubated B sulfate neutralized endotoxin effects in animals given purified at 370 and 24 hr later the small, mucoid gray, nonhemolytic endotoxin, dead endotoxin-containing organisms, and gram-nega-colonies were counted, tive septicemic animals (3,6,8,(12)(13)(14)(15). The antiendotoxin effect ~~~~~i~i~~d plasma was obtained by ofthe blood of the antibiotic appears to be separate from its antimicrobial at 150 at 40 for 10 min, ~h~ plasma was divided equally and effects.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of Polymyxin B Sulfate on Endotoxin Activity in a Gram-Negative Septicemia Model

Corrigan

Kiernat

1979

Pediatr Res

View full text Add to dashboard Cite

Summarv polymyxin B has antiendotoxin activity which is distinct from itsThe antiendotoxin effect of polymyxin B was investigated in experimentally induced septicemia in rabbits. The Pasteurella multocida organisms were sensitive to the antibacterial action of penicillin but not to polymyxin B. Animals pre-treated with polymyxin showed positive blood cultures and significantly reduced plasma endotoxin levels (Limulus test) with normal white blood cell and platelet counts when analyzed 6 hr after the injection of live organisms. Polymyxin therapy given after the animals had LntibLterial power. Heretofore, all ofthe studies that have been reported have employed either the purified lipopolysaccharide or dead gram-negative organisms. The purpose of this study was to investigate the effect of polymyxin B on endotoxin activity in a rabbit model of gram-negative septicemia. The endotoxin effects investigated were the changes in plasma endotoxin activity, and the white blood cell and platelet counts in animals who were treated with polymyxin B sulfate.established septicemia-endotoxemia reduced the plasma endotoxin levels and improved the survival, but had no effect on the leuko-MATERIALS AND METHODS penia and thrombocytopenia. The best survival data were obtained White rabbits of both sexes, California strain, weighing 1.0 kg in rabbits who were treated with both penicillin and polymyxin. were used. They were housed in an air-conditioned isolated animal The data suggest that polymyxin is effective in neutralizing the room and fed antimicrobial free rabbit chow and water ad libitum. endotoxic effects from live organisms and that the timing and The production of gram-negative septicemia in these rabbits was perhaps duration of the polymyxin treatment is of critical impor-by methods previously described (4). In essence, the animals were tance. In addition, a modified Limulus lysate method was devel-given 2 x 10"ive P. multocida organisms per kg body wt ip. The oped which showed that quantitative plasma endotoxin determi-animals regularly became clinically ill and had positive blood nation could be made more sensitive by prior heating of the plasma cultures and Limulus lysate tests 4-6 hr after the injection. Seto remove the natural inhibitors.quential blood samples were obtained from the heart and were used for blood cultures, endotoxin assay and leukocyte and platelet Speculation counts. Quantitative colony counts using heparinized whole blood were performed by pour plate technique on 5% blood agar plates his investigation and other reports have shown that ~o l~m~x i n (h4icro-~ech Diagnostics, Tucson, AZ). The plates were incubated B sulfate neutralized endotoxin effects in animals given purified at 370 and 24 hr later the small, mucoid gray, nonhemolytic endotoxin, dead endotoxin-containing organisms, and gram-nega-colonies were counted, tive septicemic animals (3,6,8,(12)(13)(14)(15). The antiendotoxin effect ~~~~~i~i~~d plasma was obtained by ofthe blood of the antibiotic appears to be separate from its antimicrobial ...

show abstract

“…This action neutralizes endotoxin effects in vitro and in vivo (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, the neutralizing effect was only seen if polymyxin B was administered in advance or in conjunction with artificially purified endotoxin.…”

mentioning

confidence: 99%

Protective Effect of Subinhibitory Polymyxin B Alone and in Combination with Ampicillin for Overwhelming Haemophilus influenzae Type B Infection in the Infant Rat: Evidence for in Vivo and in Vitro Release of Free Endotoxin after Ampicillin Treatment

1986

View full text Add to dashboard Cite

A B S T R A O . The potential endotoxin modifying effects of subinhibitory doses of polymyxin B were evaluated in an animal model of overwhelming septicemia. Five to six day old Sprague-Dawley rats were infected intraperitoneally with lo6-lo7 cfu of Haemophilus influenzae type b. At 1 2 h after infection, a t which time mortality was 1870, subinhibitory doses of polymyxin b (0.0125 mg/kg x 3 q 3 h) either alone or in combination with 500 mg/kg ampicillin significantly increased survival a t 1 7 and 20 h (p = 0.009, 0.01 and p = 0.003, 0.01) compared to animals treated with 0.5 mg/kg of ampicillin alone. Prolonged survival a t 36 h ( p = 0.009) was seen in animals receiving both ampicillin and low dose polymyxin compared to either ampicillin dose alone. Ampicillin significantly reduced the number of bacteria in blood of survivors ( p < 0.023 a t 30 min) compared to untreated animals but increased the activity of free endotoxin a t 30 min compared to controls ( p = 0.006). I n vitro endotoxin release from H. influenzae type b increased 5-fold after addition of 100 pg/rnl of ampicilin, whereas a six-fold reduction in endotoxin activity was measured after the addition of 7 pg/ml of polymyxin B. Subinhibitory doses of polymyxin B modulate the ethal effects of overwhelming H. influenzae type b infection in infant rats and might be beneficial a s adjunct treatment in gram-negative septicemia. (Pediatr Res 20: 237-241,1986 philic polysaccharide, a core, and a hydrophobic lipid component, the lipid A. The polysaccharide determines the immunological specificity of the given LPS whereas lipid A, also endowed with antigenic properties, is responsible for the biologic activities of LPS (1). The role of endotoxin in the pathogenesis of shock associated with gram-negative bacteria in humans is not clear; however, the fact that antibodies directed against the core region of LPS significantly decrease mortality in humans with gram-negative infections supports the probability of some contribution of endotoxin to the physiologic effects seen in septic shock (2).Shenep et al. (3,4) have demonstrated the release of endotoxin from Escherichia coli by antimicrobial agents in a rabbit model. Some children with Hib meningitis, who initially have normal peripheral perfusion, develop septic shock within 1 to 2 h after receiving their first dose of antibiotics. The LPS of Hib is similar in biological action to LPS from other gram-negative bacteria (5). Further indirect evidence that LPS contributes to the virulence of Hib includes the observation that antibodies against the related E. coli J5 LPS core antigen protects six to 8-wk-old mice against death due to Hib infection (6).Polymyxin B is a cationic, cyclic polypeptide antibiotic that specifically binds to the lipid A-core region of LPS, disrupting the outer membrane. This action neutralizes endotoxin effects in vitro and in vivo (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, the neutralizing effect was only seen if polymyxin B was administered in advance or in conjunction with artific...

show abstract

Modification of Human Neutrophil Response to Endotoxin with Polymyxin B Sulfate

Cited by 33 publications

References 6 publications

Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells

Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells

Effect of Polymyxin B Sulfate on Endotoxin Activity in a Gram-Negative Septicemia Model

Protective Effect of Subinhibitory Polymyxin B Alone and in Combination with Ampicillin for Overwhelming Haemophilus influenzae Type B Infection in the Infant Rat: Evidence for in Vivo and in Vitro Release of Free Endotoxin after Ampicillin Treatment

Contact Info

Product

Resources

About