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Article

Modulation of the Acute Inflammatory Response Induced by the Escherichia coli Lipopolysaccharide through the Interaction of Pentoxifylline and Florfenicol in a Rabbit Model

1
Pharmacology Laboratory, Department of Clinical Sciences, Faculty of Veterinary Sciences, Universidad de Concepción, Chillan 3820572, Chile
2
Veterinary Pathology Laboratory, Department of Pathology and Preventive Medicine, Faculty of Veterinary Sciences, Universidad de Concepción, Chillan 3820572, Chile
3
Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, California University, San Diego, CA 92182, USA
4
Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
*
Author to whom correspondence should be addressed.
Antibiotics 2023, 12(4), 639; https://doi.org/10.3390/antibiotics12040639
Submission received: 22 February 2023 / Revised: 12 March 2023 / Accepted: 22 March 2023 / Published: 24 March 2023
(This article belongs to the Special Issue Antimicrobials and Antiparasitics in Animal Health and Production)

Abstract

Background: Experimental reports have demonstrated that florfenicol (FFC) exerts potent anti-inflammatory effects, improving survival in a murine endotoxemia model. Considering the anti-inflammatory and immunomodulatory properties of pentoxifylline (PTX) as an adjuvant to enhance the efficacy of antibiotics, the anti-inflammatory effects of the interaction FFC/PTX over the E. coli Lipopolysaccharide (LPS)-induced acute inflammatory response was evaluated in rabbits. Methods: Twenty-five clinically healthy New Zealand rabbits (3.8 ± 0.2 kg body weight: bw), were distributed into five experimental groups. Group 1 (control): treated with 1 mL/4 kg bw of 0.9% saline solution (SS) intravenously (IV). Group 2 (LPS): treated with an IV dose of 5 µg/kg of LPS. Group 3 (pentoxifylline (PTX) + LPS): treated with an oral dose of 30 mg/kg PTX, followed by an IV dose of 5 µg/kg of LPS 45 min after PTX. Group 4 (Florfenicol (FFC) + LPS): treated with an IM dose of 20 mg/kg of FFC, followed by an IV dose of 5 µg/kg of LPS 45 min after FFC administration. Group 5 (PTX + FFC + LPS): treated with an oral dose of 30 mg/kg of PTX, followed by an IM dose of 20 mg/kg of FFC, and, 45 min after an IV dose of 5 µg/kg of LPS was administered. The anti-inflammatory response was evaluated through changes in plasma levels of interleukins (TNF-α, IL-1β and IL-6), C-reactive protein (CRP), and body temperature. Results: It has been shown that each drug produced a partial inhibition over the LPS-induced increase in TNF-α, IL-1β, and CRP. When both drugs were co-administered, a synergistic inhibitory effect on the IL-1β and CRP plasma concentrations was observed, associated with a synergic antipyretic effect. However, the co-administration of PTX/FFC failed to modify the LPS-induced increase in the TNF-α plasma concentrations. Conclusions: We concluded that the combination of FFC and PTX in our LPS sepsis models demonstrates immunomodulatory effects. An apparent synergistic effect was observed for the IL-1β inhibition, which peaks at three hours and then decreases. At the same time, each drug alone was superior in reducing TNF-α levels, while the combination was inferior. However, the peak of TNF-α in this sepsis model was at 12 h. Therefore, in rabbits plasma IL-1β and TNF-α could be regulated independently, thus, further research is needed to explore the effects of this combination over a more prolonged period.
Keywords: anti-inflammatory; cytokines; antibiotics; pentoxifylline; florfenicol; drug interactions anti-inflammatory; cytokines; antibiotics; pentoxifylline; florfenicol; drug interactions

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MDPI and ACS Style

Cazanga, V.; Palma, C.; Casanova, T.; Rojas, D.; Barrera, K.; Valenzuela, C.; Acevedo, A.; Ascui-Gac, G.; Pérez-Jeldres, T.; Pérez-Fernández, R. Modulation of the Acute Inflammatory Response Induced by the Escherichia coli Lipopolysaccharide through the Interaction of Pentoxifylline and Florfenicol in a Rabbit Model. Antibiotics 2023, 12, 639. https://doi.org/10.3390/antibiotics12040639

AMA Style

Cazanga V, Palma C, Casanova T, Rojas D, Barrera K, Valenzuela C, Acevedo A, Ascui-Gac G, Pérez-Jeldres T, Pérez-Fernández R. Modulation of the Acute Inflammatory Response Induced by the Escherichia coli Lipopolysaccharide through the Interaction of Pentoxifylline and Florfenicol in a Rabbit Model. Antibiotics. 2023; 12(4):639. https://doi.org/10.3390/antibiotics12040639

Chicago/Turabian Style

Cazanga, Victoria, Cristina Palma, Tomás Casanova, Daniela Rojas, Karin Barrera, Cristhian Valenzuela, Aracelly Acevedo, Gabriel Ascui-Gac, Tamara Pérez-Jeldres, and Rubén Pérez-Fernández. 2023. "Modulation of the Acute Inflammatory Response Induced by the Escherichia coli Lipopolysaccharide through the Interaction of Pentoxifylline and Florfenicol in a Rabbit Model" Antibiotics 12, no. 4: 639. https://doi.org/10.3390/antibiotics12040639

APA Style

Cazanga, V., Palma, C., Casanova, T., Rojas, D., Barrera, K., Valenzuela, C., Acevedo, A., Ascui-Gac, G., Pérez-Jeldres, T., & Pérez-Fernández, R. (2023). Modulation of the Acute Inflammatory Response Induced by the Escherichia coli Lipopolysaccharide through the Interaction of Pentoxifylline and Florfenicol in a Rabbit Model. Antibiotics, 12(4), 639. https://doi.org/10.3390/antibiotics12040639

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