title: Effects of tigecycline and doxycycline on inflammation and hemodynamics in porcine endotoxemia: a prospective, randomized, and placebo-controlled trial.
abstract: 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.
authors: *Section of Anesthesiology and Intensive Care, Department of Surgical Sciences, †Sections of Infectious Diseases and ‡Clinical Chemistry, Department of Medical Sciences, and §Section of Neurosurgery, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors: Magnus
authors: M
authors: von Seth
authors: Jan
authors: J
authors: Sjölin
authors: Anders
authors: A
authors: Larsson
authors: Mats
authors: M
authors: Eriksson
authors: Lars
authors: L
authors: Hillered
authors: Miklós
authors: M
authors: Lipcsey
mesh_terms: D000818:Animals; D004318:Doxycycline / Q000494:pharmacology*; D019446:Endotoxemia; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D013552:Swine; D000078304:Tigecycline
chemical_list: D000078304:Tigecycline; D008911:Minocycline; D004318:Doxycycline