Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia

Abstract

Antimicrobials have been used successfully for the treatment of many infectious diseases; however, the continuous increase in resistance among many bacteria in the community, as well as in the hospital setting, has led to research for new classes of antibiotics with a broader range of activity against pathogenic microorganisms (2,6,17,18). Tigecycline is a novel antibiotic, a 9-t-butylglycylamido derivative of minocyline, which inhibits protein synthesis in the presence of tetracycline-resistant, tet(M)-protected ribosomes (30); it belongs to a new semisynthetic class of antimicrobials named glycylcyclines (37). It has been shown to have activity against a wide range of microorganisms, both gram-positive and gram-negative bacteria, as well as anaerobes (16,29,39). Moreover tigecycline has activity in vitro against rapidly growing mycobacteria, such as Mycobacterium chelonae and Mycobacterium fortuitum, as well as atypical respiratory pathogens, such as Mycoplasma pneumoniae (20,21,41). In animal pneumonia models, tigecycline has been shown to have effective activity against Legionella pneumophila, Pseudomonas aeruginosa, and Streptococcus pneumoniae pulmonary infections (33).M. pneumoniae is an "atypical" bacterium that lacks a cell wall and plays an important role in acute lower respiratory tract infections in children and adults; approximately 20 to 30% of community-acquired pneumonia in the general population is due to M. pneumoniae (1,3,27,42). In the last few decades, M. pneumoniae respiratory infection has drawn increasing attention for its association with reactive airway disease and asthma (22)(23)(24). Clinical studies have shown that therapy with macrolides or tetracyclines, which are considered the drugs of choice for M. pneumoniae (11), is able to reduce the morbidity of pneumonia, shorten the duration of symptoms, and decrease the recurrence of wheezing (5,7,8,12,25,26). However, even though treatment with macrolide, ketolide, and peptide deformylase inhibitor antimicrobials significantly improves pulmonary inflammation in animal M. pneumoniae pneumonia investigations, M. pneumoniae is not eradicated from the lungs in these in vivo investigations (10,15,31,32). Of note, in these experimental investigations examining the effects of antimicrobials for M. pneumoniae pneumonia, a disassociation is often found between the microbiologic response and the significant improvement observed in other markers of disease severity. While tigecycline demonstrates in vitro activity against M. pneumoniae, tigecycline therapy in vivo for M. pneumoniae pneumonia has not been evaluated. In the present study, we investigate the effect of tigecycline on microbiologic, histologic, and immunologic (pulmonary cytokine and chemokine) parameters in our established murine model of M. pneumoniae pneumonia (9, 10, 14, 15).

Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage

“…These results are similar with the results of previous studies conducted in animal, 15 which indicate that tigecycline can reduce TNF-α plasma level. Since TNF-α is a proinflammatory cytokine, 26 the reduced plasma level could be assumed as a reflection of less inflammation process.…”

“…13,14 A new tetracycline derivative, tigecycline, reduces TNF-α level and shows neuroprotective activity in animal studies. 15 However, anti-inflammatory and neuroprotective activities of tigecycline in SSICH patients has not been well studied. This study was aimed to evaluate whether tigecycline could reduce TNF-α level as well as reduce brain injury in human subject with SSICH who underwent hematoma evacuation.…”

Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

“…All serum cytokine and chemokine levels were measured simultaneously using multiplex bead immunoassays. Multiplex bead immunoassays (Bio-Plex suspension array system; Bio-Rad Laboratories, Inc., CA, USA) were used to quantify cytokines and chemokines simultaneously by following the manufacturer's instructions (20). This novel immunoassay uses color-coded beads and permits the simultaneous detection of up to 100 cytokines and chemokines in a single well of a 96-well microplate in just 3 h (21-23).…”

Daptomycin and Tigecycline Have Broader Effective Dose Ranges than Vancomycin as Prophylaxis against a Staphylococcus aureus Surgical Implant Infection in Mice

“…In addition, in a large clinical trial for intra-abdominal infections, tigecycline and imipenem/cilastatin had similar efficacies but there was an increased incidence of postsurgical wound infections with tigecycline (7). Although the reason for these observations is unclear, tigecycline is known to induce immunosuppressive effects by decreasing cytokines and chemokines in vitro and in vivo (39,40). Thus, the decreased efficacy of tigecycline in the tissue may relate to its immunomodulatory effects, which are more likely to contribute to host defense against bacteria in tissue than bacteria in a biofilm on an implant.…”