Ketamine inhibits LPS-induced tumour necrosis factor-alpha and interleukin-6 in an equine macrophage cell line

Lankveld, D. P. K.; Bull, Sarah; Dijk, Paul van; Fink‐Gremmels, Johanna; Hellebrekers, L.J.

doi:10.1051/vetres:2004061

Cited by 42 publications

(36 citation statements)

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“…In vitro work indicates that ketamine concentrations >100 ng/mL significantly reduced the production of LPS‐induced TNF‐α and IL‐6 in equine macrophages and ketamine's dose‐dependent inhibition of LPS‐induced proinflammatory cytokines is well documented in other species 16,17,27 . The typical ketamine anesthetic induction dose used in horses (2.2 mg/kg) can result in peak plasma levels >5,000 ng/mL, with CNS dissociative effects occurring at 800 ng/mL and anesthetic recovery beginning when plasma levels decline below 1,000 ng/mL 19,28,29 . In the this study, the KET group attained plasma ketamine concentrations >200 ng/mL throughout the study period with 1 horse exceeding 500 ng/mL at 5 hours f‐LPS.…”

Section: Discussionmentioning

confidence: 68%

“…Immunomodulating properties of subanesthetic ketamine in horses during experimental endotoxemia have not been investigated in vivo. The potential of ketamine to attenuate the inflammatory and immune responses in endotoxemic horses is supported by previous reports 18,19 . Hence, we hypothesized that a subanesthetic ketamine continuous rate infusion (CRI) can safely be administered to conscious horses and attenuate the clinical, inflammatory, and immunologic responses in an experimental model of endotoxemia in healthy horses.…”

mentioning

confidence: 79%

“…Additionally, ketamine has positive immunomodulating and anti‐inflammatory effects during periods of experimental endotoxemia and septic shock in rats 15,16 . Specifically, ketamine down‐regulates nuclear factor kappa B (NFκB) signaling, decreases inflammatory cytokine production (TNF‐α, interleukin‐6 [IL‐6]), and suppresses platelet aggregation in mouse, human, and equine cell lines after exposure to LPS 17–20 . Furthermore, in vitro ketamine inhibits COX‐2 expression in rats 21 .…”

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confidence: 99%

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Clinical and Immunomodulating Effects of Ketamine in Horses with Experimental Endotoxemia

Alcott

Sponseller

Wong

et al. 2011

Veterinary Internal Medicne

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Background: Ketamine has immunomodulating effects both in vitro and in vivo during experimental endotoxemia in humans, rodents, and dogs.Hypothesis: Subanesthetic doses of ketamine will attenuate the clinical and immunologic responses to experimental endotoxemia in horses.Animals: Nineteen healthy mares of various breeds. Methods: Experimental study. Horses were randomized into 2 groups: ketamine-treated horses (KET; n 5 9) and salinetreated horses (SAL; n 5 10). Both groups received 30 ng/kg of lipopolysaccharide (LPS, Escherichia coli, O55:B5) 1 hour after the start of a continuous rate infusion (CRI) of racemic ketamine (KET) or physiologic saline (SAL). Clinical and hematological responses were documented and plasma concentrations of tumor necrosis factor-a (TNF-a) and thromboxane B 2 (TXB 2 ) were quantified.Results: All horses safely completed the study. The KET group exhibited transient excitation during the ketamine loading infusion (P o .05) and 1 hour after discontinuation of administration (P o .05). Neutrophilic leukocytosis was greater in the KET group 8 and 24 hours after administration of LPS (P o .05). Minor perturbations of plasma biochemistry results were considered clinically insignificant. Plasma TNF-a and TXB 2 production peaked 1.5 and 1 hours, respectively, after administration of LPS in both groups, but a significant difference between treatment groups was not demonstrated.Conclusions and Clinical Importance: A subanesthetic ketamine CRI is well tolerated by horses. A significant effect on the clinical or immunologic response to LPS administration, as assessed by clinical observation, hematological parameters, and TNF-a and TXB 2 production, was not identified in healthy horses with the subanesthetic dose of racemic ketamine utilized in this study.

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Section: Discussionmentioning

confidence: 68%

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confidence: 79%

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confidence: 99%

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Clinical and Immunomodulating Effects of Ketamine in Horses with Experimental Endotoxemia

Alcott

Sponseller

Wong

et al. 2011

Veterinary Internal Medicne

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“…, 1979), but was within the range of concentrations that exhibit analgesic effects in humans (Hocking & Cousins, 2003; Strigo et al. , 2005) and anti‐inflammatory actions in vitro (Lankveld et al. , 2005).…”

Section: Discussionmentioning

confidence: 98%

“…, 2005). In an equine macrophage cell line, KET inhibited LPS‐induced TNF‐ α and IL‐6 responses in a concentration‐dependent manner (Lankveld et al. , 2005), demonstrating that this drug could have cytokine‐modulating effects in horses suffering from systemic inflammation and endotoxemia.…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic effects and pharmacokinetic profile of a long‐term continuous rate infusion of racemic ketamine in healthy conscious horses

Lankveld

Driessen

Soma

et al. 2006

Vet Pharm & Therapeutics

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effects and pharmacokinetic profile of a long-term continuous rate infusion of racemic ketamine in healthy conscious horses. J. vet. Pharmacol. Therap. 29,[477][478][479][480][481][482][483][484][485][486][487][488] Ketamine (KET) possesses analgesic and anti-inflammatory activity at subanesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, nonesterified fatty acids, and muscle enzyme levels were measured, as were plasma concentrations of KET and its metabolites using liquid chromatographytandem mass spectrometry (LC-MS/MS). Levels of sedation and muscle tension were scored. Respiration and heart rate significantly increased during the early infusion phase. Glucose and cortisol significantly varied both during and after infusion. During CRI all horses scored 0 on sedation. All but one horse scored 0 on muscle tension, with one mare scoring 1. All other parameters remained within or close to physiological limits without significant changes from pre-CRI values. The mean plasma concentration of KET during the 1.5 mg/kg/h KET CRI was 235 ng/mL. The decline of its plasma concentration-time curve of both KET and norketamine (NKET) following the CRI was described by a twocompartmental model. The metabolic cascade of KET was NKET, hydroxynorketamine (HNK), and 5,6-dehydronorketamine (DHNK). The KET median elimination half-lives (t 1/2a and t 1/2b ) were 2.3 and 67.4 min, respectively. The area under the KET plasma concentration-time curve (AUC), elimination was 76.0 lgAEmin/mL. Volumes of C 1 and C 2 were 0.24 and 0.79 L/kg, respectively. It was concluded that a KET CRI of 1.5 mg/kg/h can safely be administered to healthy conscious horses for at least 6 h, although a slight modification of the initial infusion rate regimen may be indicated. Furthermore, in the horse KET undergoes very rapid biotransformation to NKET and HNK and DHNK were the major terminal metabolites.(Paper

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Pain Management in Critical Patients

Karas

2018

Textbook of Small Animal Emergency Medicine

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Ketamine inhibits LPS-induced tumour necrosis factor-alpha and interleukin-6 in an equine macrophage cell line

Cited by 42 publications

References 18 publications

Clinical and Immunomodulating Effects of Ketamine in Horses with Experimental Endotoxemia

Clinical and Immunomodulating Effects of Ketamine in Horses with Experimental Endotoxemia

Pharmacodynamic effects and pharmacokinetic profile of a long‐term continuous rate infusion of racemic ketamine in healthy conscious horses

Pain Management in Critical Patients

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