In previous studies,
tetracyclines have been shown to decrease the release of
cytokines in experimental settings of endotoxaemia.
Tigecycline is the first member of the closely related glycylglycines and, due to its broad antimicrobial spectrum, it is considered useful in the treatment of
sepsis. We therefore tested its ability to influence the concentrations of the proinflammatory
cytokines interleukin (IL)-1beta, tumour
necrosis factor-alpha (
TNFalpha) and
IL-6 in an established ex vivo model of human endotoxaemia. Whole blood from ten healthy volunteers was incubated with either saline (negative control),
tigecycline (1 microg/mL [therapeutic concentration] or 100 microg/mL [supratherapeutic concentration]),
lipopolysaccharide (LPS; 50 pg/mL, control) or a combination of
tigecycline plus LPS (test group). Concentrations of IL-1beta,
TNFalpha and
IL-6 in the supernatant were measured using commercially available
enzyme-linked
immunosorbent assay (ELISA) kits. As expected, incubation with LPS significantly increased the
cytokine concentrations in whole blood compared with baseline (P<0.05). The combination of
tigecycline plus LPS did not exert any significant effect on the concentrations of IL-1beta,
IL-6 and
TNFalpha after 2h and 4h of incubation compared with LPS alone. These results indicate that proinflammatory
cytokines remained unaffected by
tigecycline in an established ex vivo model of systemic inflammatory response.