Anti-inflammatory effects of the antibiotics ceftazidime and tobramycin in porcine endotoxin shock: are they really anti-inflammatory? Authors' response
Critical Care volume 8, Article number: 141 (2004)
We would like to thank Dr Wiedermann for his interest in our paper .
It is well established that IL-6 has been associated with anti-inflammatory properties, as pointed out by Dr Wiedermann. Although not a proinflammatory cytokine, IL-6 is produced by several cells as a result of previous stimulation by tumour necrosis factor (TNF)-α and IL-1. Therefore, the concentration of IL-6 has been considered to be a marker of the inflammatory reaction, as well as the preceding TNF-α and IL-1 responses, and in several studies it was shown to correlate with prognosis in patients with severe sepsis and septic shock [2–4]. Furthermore, persistently elevated levels of IL-6 have been associated with the development of multiple organ dysfunction syndrome .
The primary end-point of our study was to investigate whether the biological effects of endotoxin, as measured using TNF-α and IL-6 responses, could be neutralized by antibiotics. The early peak cytokine response after 1 hour (for TNF-α) and 2 hours (for IL-6) was chosen because both antibiotics in vitro had been shown to induce protection against oxidative injury, which induces an inflammatory response that might influence the results. A secondary end-point was whether the antibiotic treatment could affect cytokine concentrations in an animal model. The lower concentration of IL-6 during the last period of the experiment might be consistent with a reduction in oxidative stress and a concomitant proinflammatory response. In comparison with IL-6, the TNF-α response is often of lesser magnitude and of more transient character, which increases the statistical β error and makes it more difficult to demonstrate a reduction even if there is one.
It was emphasized that our data did not rule out other mechanisms. However, even if IL-6 does not have proinflammatory properties per se, then the most likely explanation was that IL-6 indicated the presence of an inflammatory response and that the reduction in IL-6 represented an anti-inflammatory effect caused by tobramycin and ceftazidime.
tumour necrosis factor.
Wiedermann F: Anti-inflammatory effects of the antibiotics ceftazidime and tobramycin in porcine endotoxin shock: are they really anti-inflammatory? [Letter.]. Crit Care 2004, in press.
Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T: The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin-6, interleukin-1 and fatal outcome. J Exp Med 1989, 169: 333-338.
Casey LC, Balk RA, Bone RC: Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 1993, 119: 771-778.
Reinhart K, Bayer O, Brunkhorst F, Meisner M: Markers of endothelial damage in organ dysfunction and sepsis. Crit Care Med 2002, Suppl: 302-312. 10.1097/00003246-200205001-00021
Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn RJ, Dupont E: Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest 1993, 103: 565-575.
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Goscinski, G., Lipcsey, M., Eriksson, M. et al. Anti-inflammatory effects of the antibiotics ceftazidime and tobramycin in porcine endotoxin shock: are they really anti-inflammatory? Authors' response. Crit Care 8, 141 (2004). https://doi.org/10.1186/cc2815
- Septic Shock
- Severe Sepsis
- Organ Dysfunction