Cutting Edge: Fever-Associated Temperatures Enhance Neutrophil Responses to Lipopolysaccharide: A Potential Mechanism Involving Cell Metabolism

Rosenspire, Allen J.; Kindzelskii, Andrei L.; Petty, Howard R.

doi:10.4049/jimmunol.169.10.5396

Cited by 53 publications

(31 citation statements)

References 22 publications

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“…Finally, maintaining a normal core body temperature (36.6 Ϯ 0.5°C) after anesthesia has been shown to decrease the incidence of infectious complications in patients undergoing colorectal resection (16). Among the mechanisms suggested in the antibacterial effect of heating, augmentation of the innate immune function is probably the most intensively studied (9,10,17,19,27). Though our results demonstrate that the application of AMFields and sham heat did not cause an increase in lung temperatures, these treatments did raise the temperature of the peripheral organs of the treated mice by at least 2 degrees (the normal skin temperature of mice is 34 to 35°C, while in the present study, the electrode temperature was set to 37°C).…”

Section: Discussionmentioning

confidence: 99%

Microbial Growth Inhibition by Alternating Electric Fields in Mice withPseudomonas aeruginosaLung Infection

Giladi

Porat²,

Blatt³

et al. 2010

Antimicrob Agents Chemother

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High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2°C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality.The 20th century was the golden era of the antibacterial agents, with millions of people owing their lives to the discovery of and treatment with the numerous antibiotic families used today. Surely, antibacterial agents will continue to play a major role in the battle against pathogenic bacteria in the 21st century; however, the extensive use of antibiotics holds a threat of a far less optimistic future due to the rapid rise of multidrugresistant bacteria. Recently, the potential use of physical means as an aid to antibiotics in the battle against bacterial pathogens has been studied: photodynamic therapy (12, 21, 35), ultrasound wave therapy (7,23,25), thermotherapy (26), and weak electric currents (4,6,24,32,33) are all being tested as treatment modalities against pathogenic microorganisms. The major drawback of the methods mentioned above is their low therapeutic index due to the high levels of heating produced by ultrasonic waves, thermotherapy, and photodynamic therapy (36) and the activated oxygen generated by photodynamic therapy, both of which can damage the tissues in and around the target area (22). In addition, the use of conductive electrodes for the generation of electric currents is associated with the release of metal ions and free radicals at the electrode surface, all of which are toxic to living cells (18). Indeed, as of today, none of the above-mentioned means has matured into an approved treatment modality against bacterial pathogens.Recently, we demonstrated that low-intensity alternating electric fields of high frequencies (antimicrobial fields [AMFields]) have an in vitro inhibitory effect on the growth of pathogenic bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa (8). AMFields were generated using electrically insulated electrodes and therefore were not associated with the production of free radicals, toxic metal ions, or electrolysis at the electrode surface. Fields of the relatively high frequency at which the AMFields effects were observed (with an optimum at 10 MHz) have no known effect on human cells (13,14). Indeed, we found that AMFields have no effect on the growth of cell cultures in vitro (unpublished results). Furthermore, the high frequencies of the AMFields allow for the application of relatively h...

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Section: Discussionmentioning

confidence: 99%

Microbial Growth Inhibition by Alternating Electric Fields in Mice withPseudomonas aeruginosaLung Infection

Giladi

Porat²,

Blatt³

et al. 2010

Antimicrob Agents Chemother

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“…These animals were not only subjected to a greater intrapulmonary PMN burden, but they also were exposed to higher levels of the PMN activating cytokines, GM-CSF, KC, MIP-2, and IL-1␤. Furthermore, FRH itself directly enhances PMN generation of reactive oxygen intermediates and NO responsiveness to LPS (48). In fact, we previously reported that immunoblockade of the common receptor for KC and MIP-2 in hyperoxia-exposed mice partially reversed the accelerated death caused by coexposure to FRH (24).…”

Section: Figurementioning

confidence: 90%

Febrile-Range Hyperthermia Augments Neutrophil Accumulation and Enhances Lung Injury in Experimental Gram-Negative Bacterial Pneumonia

Rice

Martin

et al. 2005

The Journal of Immunology

101

109

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We previously demonstrated that exposure to febrile-range hyperthermia (FRH) accelerates pathogen clearance and increases survival in murine experimental Klebsiella pneumoniae peritonitis. However, FRH accelerates lethal lung injury in a mouse model of pulmonary oxygen toxicity, suggesting that the lung may be particularly susceptible to injurious effects of FRH. In the present study, we tested the hypothesis that, in contrast with the salutary effect of FRH in Gram-negative peritonitis, FRH would be detrimental in multilobar Gram-negative pneumonia. Using a conscious, temperature-clamped mouse model and intratracheal inoculation with K. pneumoniae Caroli strain, we showed that FRH tended to reduce survival despite reducing the 3 day-postinoculation pulmonary pathogen burden by 400-fold. We showed that antibiotic treatment rescued the euthermic mice, but did not reduce lethality in the FRH mice. Using an intratracheal bacterial endotoxin LPS challenge model, we found that the reduced survival in FRH-treated mice was accompanied by increased pulmonary vascular endothelial injury, enhanced pulmonary accumulation of neutrophils, increased levels of IL-1β, MIP-2/CXCL213, GM-CSF, and KC/CXCL1 in the bronchoalveolar lavage fluid, and bronchiolar epithelial necrosis. These results suggest that FRH enhances innate host defense against infection, in part, by augmenting polymorphonuclear cell delivery to the site of infection. The ultimate effect of FRH is determined by the balance between accelerated pathogen clearance and collateral tissue injury, which is determined, in part, by the site of infection.

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“…The febrile rise in body temperature could exert beneficial effects for the host by enhancing immune cell activities (138) and making the internal thermal environment out of the temperature range optimal for pathogen growth (90). Increase in body temperature similar to fever is also observed when animals receive psychological stress.…”

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confidence: 94%

Central circuitries for body temperature regulation and fever

Nakamura

2011

American Journal of Physiology-Regulatory, Integrative and Comp

442

394

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Nakamura K. Central circuitries for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol 301: R1207-R1228, 2011. First published September 7, 2011 doi:10.1152/ajpregu.00109.2011.-Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonshivering thermogenesis in brown adipose tissue, shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation, heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend thermal homeostasis from environmental thermal challenges, feedforward thermosensory information on environmental temperature sensed by skin thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus to the preoptic area (POA). The POA also receives feedback signals from local thermosensitive neurons, as well as pyrogenic signals of prostaglandin E 2 produced in response to infection. These afferent signals are integrated and affect the activity of GABAergic inhibitory projection neurons descending from the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic and somatic premotor neurons in the rMR, which then drive spinal motor output mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction. Warming signals enhance the descending inhibition from the POA to inhibit the motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis. This central thermoregulatory mechanism also functions for metabolic regulation and stress-induced hyperthermia.

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Cutting Edge: Fever-Associated Temperatures Enhance Neutrophil Responses to Lipopolysaccharide: A Potential Mechanism Involving Cell Metabolism

Cited by 53 publications

References 22 publications

Microbial Growth Inhibition by Alternating Electric Fields in Mice withPseudomonas aeruginosaLung Infection

Microbial Growth Inhibition by Alternating Electric Fields in Mice withPseudomonas aeruginosaLung Infection

Febrile-Range Hyperthermia Augments Neutrophil Accumulation and Enhances Lung Injury in Experimental Gram-Negative Bacterial Pneumonia

Central circuitries for body temperature regulation and fever

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