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Letter

Anti-inflammatory effects of the antibiotics ceftazidime and tobramycin in porcine endotoxin shock: are they really anti-inflammatory? Authors' response

Gunilla Goscinski1*, Miklos Lipcsey2, Mats Eriksson3, Anders Larsson4, Eva Tano5 and Jan Sjölin6

Author Affiliations

1 MD, Section of Infectious Diseases, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

2 MD, Department of Anesthesiology and Intensive Care, Gävle-Sandviken County Hospital, Gävle, Sweden

3 Associate Professor, Section of Anesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden

4 Associate Professor, Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

5 Biomedical Scientist, Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

6 Associate Professor, Section of Infectious Diseases, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

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Critical Care 2004, 8:141 doi:10.1186/cc2815


The electronic version of this article is the complete one and can be found online at:


Published:5 February 2004

© 2004 BioMed Central Ltd

Letter

We would like to thank Dr Wiedermann for his interest in our paper [1].

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 [5].

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.

Competing interests

None declared.

Abbreviations

IL = interleukin; TNF = tumour necrosis factor.

References

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    Crit Care 2004, in press. OpenURL

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    J Exp Med 1989, 169:333-338. PubMed Abstract OpenURL

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    Ann Intern Med 1993, 119:771-778. PubMed Abstract | Publisher Full Text OpenURL

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    Crit Care Med 2002, Suppl:302-312. Publisher Full Text OpenURL

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    Chest 1993, 103:565-575. PubMed Abstract OpenURL