Tigecycline has no effect on cytokine release in an ex vivo endotoxin model of human whole blood

Traunmüller, Friederike; Thallinger, Christiane; Hausdorfer, Johann; Lambers, Christopher; Tzaneva, Stanislava; Kampitsch, Thomas; Endler, Georg; Joukhadar, Christian

doi:10.1016/j.ijantimicag.2008.11.008

Cited by 4 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies demonstrated no effect of tigecycline on TNF-! release from endotoxin-stimulated human leukocytes (23,24). In what way tigecycline inhibits release of TNF-!…”

Section: Previous Studiesmentioning

confidence: 99%

Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia

Seth¹,

Sjölin²,

Larsson³

et al. 2015

Shock

View full text Add to dashboard Cite

Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from gram-negative multiresistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have not been previously explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison with doxycycline and placebo. Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg, or placebo and subjected to 6-h endotoxin infusion at 0.5 μg kg(-1) h(-1). Markers of inflammation, nitric oxide production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism, and acid-base parameters were monitored. Peak plasma tumor necrosis factor-α was lower in the doxycycline group (P = 0.031) but not in the tigecycline group (P = 0.86) compared with placebo, with geometric mean plasma concentrations of 16, 79, and 63 ng mL(-1), respectively. Mean arterial pressure was higher 4 to 6 h in the tigecycline group, with values at 6 h of 107 ± 9 mmHg compared with the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively; P = 0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group but not in the tigecycline group at 4 to 6 h (P = 0.009 and P = 0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism, and acid-base parameters were unaffected by tigecycline. Consistent with known anti-inflammatory properties, doxycycline yielded decreased tumor necrosis factor-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.

show abstract

“…Other studies demonstrated no effect of tigecycline on TNF-! release from endotoxin-stimulated human leukocytes (23,24). In what way tigecycline inhibits release of TNF-!…”

Section: Previous Studiesmentioning

confidence: 99%

Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia

Seth¹,

Sjölin²,

Larsson³

et al. 2015

Shock

View full text Add to dashboard Cite

show abstract

“…(30) More specifically, Krakauer and Buckley showed that doxycycline inhibited in a dose dependent manner the production of cytokines TNF-, IL1, and IL-6 by PBMC stimulated by SEB and TSST-1. (31) Although initial reports indicated that proinflammatory cytokines remained unaffected by tigecycline in an established ex vivo model of systemic inflammatory response, (32) a recent investigation involving a murine model of Mycoplasma pneumonia corroborated our findings by showing a lower BAL cytokine concentrations of IL-1, IL-12 (p40/p70), IFN-, and TNF-, and chemokines MIG, MIP-1, and IP-10 in a murine model of Mycoplasma pneumoniae-infected mice treated with tigecycline. (33) A number of investigations have shown that antimicrobial agents which can affect pathways of inflammation accumulate in inflammatory cells at concentrations up to several hundred-fold higher than those in extracellular fluid.…”

Section: Discussionmentioning

confidence: 99%

Tigecycline attenuates staphylococcal superantigen-induced T-cell proliferation and production of cytokines and chemokines

Saliba

Paasch

Solh

2009

Immunopharmacology and Immunotoxicology

View full text Add to dashboard Cite

The purpose of this study is to examine the in vitro modulatory effect of tigecycline on staphylococcal superantigen-induced T-cell activation and cytokines and chemokines production by human peripheral blood mononuclear cells (PBMC). Isolated human PBMC from ten healthy volunteers were stimulated by staphylococcal enterotoxin B (SEB) and Staphylococcal toxic shock syndrome toxin-1 (TSST-1) superantigens with varying concentrations of tigecycline. Cytokines IL-1 beta, IL-6, TNF-alpha, and chemokines MIP-1 alpha and MIP-1 beta concentrations were measured along with T cell proliferation. Results demonstrated that tigecycline alters cytokine production and reduces T-cell proliferation in vitro suggesting an immunomodulatory activity independent of its antimicrobial effect.

show abstract

“…In in vivo and ex vivo murine models, T-helper (Th)-1 cytokines, but not Th-2 cytokines, were suppressed (11,12). Inhibition of T-cell proliferation was seen when TGC was co-cultured with S. aureus antigen (13) but not with endotoxin lipopolysaccharide (LPS) (14). Despite its inhibitory activity on Th-1, it did not affect production of Th-2 dependent antibodies in B cells (11).…”

Section: Immunomodulatory Effects Of Tigecycline In Balb/c Micementioning

confidence: 99%

Immunomodulatory Effects of Tigecycline in Balb/C Mice

Elhayek

Fararjeh²,

Assaf

et al. 2018

Acta Pharmaceutica

View full text Add to dashboard Cite

Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We t herefore i nvestigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3-5 mmol L-1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation.

show abstract

Tigecycline has no effect on cytokine release in an ex vivo endotoxin model of human whole blood

Cited by 4 publications

References 15 publications

Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia

Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia

Tigecycline attenuates staphylococcal superantigen-induced T-cell proliferation and production of cytokines and chemokines

Immunomodulatory Effects of Tigecycline in Balb/C Mice

Contact Info

Product

Resources

About