Ceftiofur Regulates LPS-Induced Production of Cytokines and Improves LPS-Induced Survival Rate in Mice
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Ceftiofur Regulates LPS-Induced Production of Cytokines and Improves LPS-Induced Survival Rate in Mice Xinxin Ci,1 Hongyu Li,1 Yu Song,1 Na An,1 Qinlei Yu,1 Fanqin Zeng,1 and Xuming Deng1,2
Abstract—The influence of ceftiofur on immune responses has been suggested by results of in vitro studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. To investigate the treatment of endotoxic mice with ceftiofur, mice were pretreated with ceftiofur at different times before and after challenge with a lethal dose of 30 mg/kg lipopolysaccharide (LPS). We found that 20 mg/kg ceftiofur had a significant protective effect and reduced the mortality of mice at early stages. To further understand the mechanism of action of ceftiofur, we examined plasma cytokine levels. Mice treated with LPS alone showed markedly increased plasma levels of TNF-α, IL-1β, IL-6 and IL-10, whereas mice pretreated with 20 mg/kg ceftiofur showed significantly decreased plasma levels of TNF-α, IL-1β and IL-6, but increased plasma levels of IL-10. These results support the idea that ceftiofur has a beneficial effect on LPS-induced endotoxemia caused by LPS through its modulation of cytokine levels. This confirms the effect of ceftiofur for the treatment of endotoxemia, which is caused by a Gram-negative bacterial infection. KEY WORDS: ceftiofur; LPS; cytokines; survival rate; mice.
and production of cytokines [5–7]. In particular, it has been shown that cephalosporins reduce the production of proinflammatory cytokines, like tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß), in response to lipopolysaccharide (LPS) in vitro [3]. In this regard, it has been suggested that the anti-inflammatory action, but not the antimicrobial activity of cephalosporins, is responsible for the clinical effectiveness of these compounds in chronic inflammatory disorders. Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use. It has been known to have many pharmacological activities, including anti-microbial and anti-inflammatory activities [8]. It has been widely used to treat a broad array of infectious diseases caused by Gram-positive and Gram-negative bacteria, such as pneumonia, peritonitis and mastitis in dairy cattle [8, 9]. We have previously shown that ceftiofur can inhibit LPS-stimulated TNF-α, IL-1β and IL-6 secretion in RAW264.7 cells via activation of the NF-κB and MAP-kinase pathways [10]. Although these
INTRODUCTION Cephalosporins, such as cefodizime, are a wellestablished class of antibacterial agents that are active against many Gram-positive and some Gram-negative bacteria [1]. Beyond their antibacterial activity, these compounds are reported to exert anti-inflammatory and immunomodulatory activity in vitro and in vivo [2–4]. It has been reported previously that antimicrobials can affect several steps in the inflammatory process, such as migration of neutrophils, modulation of oxidative burst
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Department of Veterinary Pha
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