Evidence of Less Severe Aortic Valve Destruction after Treatment of Experimental Staphylococcal Endocarditis with Vancomycin and Dexamethasone

Siaperas, Petros; Pefanis, Angelos; Iliopoulos, Dimitrios; Katsarolis, Ioannis; Kyroudi-Voulgari, Aspassia; Donta, Ismini; Karayiannakos, Panayiotis; Giamarellou, Helen

doi:10.1128/aac.45.12.3531-3537.2001

Cited by 11 publications

(15 citation statements)

References 37 publications

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“…In contrast, potential beneficial effects of corticoids on leukocyte recruitment in gram-positive bacterial toxin-induced inflammation have largely been neglected previously. Nonetheless, one study reported that SEA-provoked neutrophil migration is negatively regulated by dexamethasone treatment (9), and more recent data from an experimental study of staphylococcal endocarditis in rabbits demonstrated that there was reduced neutrophil infiltration or aortic valve destruction after combined treatment with vancomycin and dexamethasone (32). However, the anti-inflammatory mechanisms of action of dexamethasone in superantigen-induced inflammation remain elusive.…”

Section: Fig 4 Time-dependent Leukocyte Response To Seb Animals Rementioning

confidence: 98%

“…We and other workers have previously demonstrated that treatment with dexamethasone reduces the expression and function of chemokines in response to pro-inflammatory cytokines and thus attenuates leukocyte adhesion and recruitment (16,32,34,42). On the one hand, production of inflammatory mediators and recruitment of leukocytes in response to a gram-negative bacterial toxin, such as lipopolysaccharide, have been extensively studied and, in most reports, have been shown to be sensitive to glucocorticoid treatment (30,40,41).…”

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confidence: 99%

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Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2

Schramm

Thorlacius

2003

Infect Immun

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This study was conducted to examine the anti-inflammatory mechanisms of dexamethasone during leukocyte recruitment and expression of the CXC chemokines macrophage inflammatory protein 2 (MIP-2) (CXCL2) and cytokine-induced neutrophil chemoattractant (KC) (CXCL1) in staphylococcal enterotoxin B (SEB)-induced acute inflammation. To do this, SEB was injected into murine air pouches with or without dexamethasone pretreatment for 2 h. SEB induced infiltration of leukocytes in a dose-and time-dependent manner, with the maximal response observed after 4 h of treatment with 10 g of SEB. The recruited leukocytes comprised more than 77% neutrophils. Moreover, SEB challenge (10 g) provoked time-dependent secretion of CXC chemokines, which peaked after 1 h. Local administration of antibodies against MIP-2 and KC significantly reduced SEB-triggered neutrophil accumulation by 38 and 59%, respectively. Dexamethasone (10 mg kg ؊1 ) significantly decreased neutrophil recruitment by 82% and reduced secretion of MIP-2 and KC by 89 and 85%, respectively, in response to SEB challenge. Our data demonstrate that dexamethasone potently inhibits neutrophil recruitment in SEB-induced inflammation. Moreover, we provide evidence that MIP-2 and KC are key mediators in the neutrophil response to SEB. Furthermore, our findings demonstrate that dexamethasone attenuates SEB-induced expression of MIP-2 and KC. Thus, this study elucidates important signaling pathways of SEB-induced neutrophil recruitment and anti-inflammatory mechanisms of action of dexamethasone.

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Section: Fig 4 Time-dependent Leukocyte Response To Seb Animals Rementioning

confidence: 98%

mentioning

confidence: 99%

Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2

Schramm

Thorlacius

2003

Infect Immun

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“…The rabbit model of aortic valve endocarditis was used to evaluate treatment regimens (10,26). The study received a permit from the Veterinary Directorate of the Prefecture of Athens in conformance with Greek legislation in response to EU directive 160/1991.…”

Section: Methodsmentioning

confidence: 99%

“…In one report on experimental MRSA endocarditis, it was found that, immediately after the end of treatment, the severity of valve tissue damage was significantly less in the group receiving dexamethasone (26). However, the possibility that the steroids might delay valve destruction but not prevent it could not be excluded.…”

mentioning

confidence: 99%

Dexamethasone as Adjuvant Therapy to Moxifloxacin Attenuates Valve Destruction in Experimental Aortic Valve Endocarditis Due to Staphylococcus aureus

Skiadas

Pefanis

Papalois

et al. 2007

Antimicrob Agents Chemother

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Although the beneficial effects of dexamethasone have frequently been investigated in various serious-infection settings, insufficient data on valve histology and cardiac function for infective endocarditis are available. The efficacy of moxifloxacin for the treatment of experimental aortic valve endocarditis due to methicillin-susceptible Staphylococcus aureus and the long-term effects of dexamethasone were evaluated in the current study. Sixty-eight rabbits were randomly assigned to four groups: A, B, C, and D. Group A consisted of 18 animals and functioned as a control group. Groups B and C consisted of 11 and 23 subjects, respectively, which received moxifloxacin for 5 days in a human-like pharmacokinetic simulation. Group D consisted of 16 animals that were administered moxifloxacin plus dexamethasone (0.25 mg/kg of body weight twice a day intravenously). The group B animals were sacrificed a day after the completion of treatment, and group C and D animals were sacrificed after 12 days in order to monitor any possible relapse and allow microbiological, histopathological, and echocardiographic evaluation of the longterm effects of glucocorticoids. No differences in survival, sterilization rates, or inflammatory infiltration and calcification of valve tissue were observed among the treated groups. However, the degrees of valve damage and collagenization were significantly worse, the fibroblast content was higher, and fractional shortening of the left ventricle fluctuated significantly in group C compared to group D (all groups, P < 0.05). We concluded that dexamethasone treatment for experimental S. aureus endocarditis attenuates valve destruction and preserves overall cardiac function without impeding the efficacy of moxifloxacin.

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“…For those infections within or just below the skin, as well as nonbiofilm septic infections, a robust innate and adaptive inflammatory response seems necessary for clearance. However, in other locations, such as the intramedullary bone infection model in mice (35) and cases of osteomyelitis (29), endocarditis (44), and endophthalmitis (14), a robust response walls the infection off to prevent systemic spread. However, it also forms a nidus of infection that promotes chronic and progressive tissue damage and occasional escape and seeding of other areas.…”

Section: Vol 79 2011 Immune Response To S Aureus Biofilm Infectionmentioning

confidence: 99%

Suppression of the Inflammatory Immune Response Prevents the Development of Chronic Biofilm Infection Due to Methicillin-Resistant Staphylococcus aureus

et al. 2011

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Staphylococcus aureus is a common cause of prosthetic implant infections, which can become chronic due to the ability of S. aureus to grow as a biofilm. Little is known about adaptive immune responses to these infections in vivo. We hypothesized that S. aureus elicits inflammatory Th1/Th17 responses, associated with biofilm formation, instead of protective Th2/Treg responses. We used an adapted mouse model of biofilm-mediated prosthetic implant infection to determine chronic infection rates, Treg cell frequencies, and local cytokine levels in Th1-biased C57BL/6 and Th2-biased BALB/c mice. All C57BL/6 mice developed chronic S. aureus implant infection at all time points tested. However, over 75% of BALB/c mice spontaneously cleared the infection without adjunctive therapy and demonstrated higher levels of Th2 cytokines and anti-inflammatory Treg cells. When chronic infection rates in mice deficient in the Th2 cytokine interleukin-4 (IL-4) via STAT6 mutation in a BALB/c background were assessed, the mice were unable to clear the S. aureus implant infection. Additionally, BALB/c mice depleted of Treg cells via an anti-CD25 monoclonal antibody (MAb) were also unable to clear the infection. In contrast, the C57BL/6 mice that were susceptible to infection were able to eliminate S. aureus biofilm populations on infected intramedullary pins once the Th1 and Th17 responses were diminished by MAb treatment with anti-IL-12 p40. Together, these results indicate that Th2/Treg responses are mechanisms of protection against chronic S. aureus implant infection, as opposed to Th1/Th17 responses, which may play a role in the development of chronic infection.

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Evidence of Less Severe Aortic Valve Destruction after Treatment of Experimental Staphylococcal Endocarditis with Vancomycin and Dexamethasone

Cited by 11 publications

References 37 publications

Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2

Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2

Dexamethasone as Adjuvant Therapy to Moxifloxacin Attenuates Valve Destruction in Experimental Aortic Valve Endocarditis Due to Staphylococcus aureus

Suppression of the Inflammatory Immune Response Prevents the Development of Chronic Biofilm Infection Due to Methicillin-Resistant Staphylococcus aureus

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