Research

Anti-L-selectin antibody therapy does not worsen the postseptic course in a baboon model

Heinz R Redl¹ , Ulrich Martin² , Anna Khadem³ , Linda E Pelinka⁴ and Martijn van Griensven⁵

¹Professor, Director, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13, A-1200 Vienna, Austria

²Managing director, La Merie S.L., Passatge Jordi Ferran, 20, E-08028 Barcelona, Spain

³Senior technical assistant, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13, A-1200 Vienna, Austria

⁴Assistant professor, consultant anesthesiologist, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13, A-1200 Vienna, Austria

⁵Professor, associate director, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13, A-1200 Vienna, Austria

author email corresponding author email

Critical Care 2005, 9:R735-R744doi:10.1186/cc3825

Published:	8 November 2005

Abstract

Introduction

Anti-adhesion molecule therapy prevents leukocytes from extravasating. During exaggerated inflammation, this effect is wanted; however, during infection, blocking diapedesis may be detrimental. In this study, therefore, the potential risks of anti-L-selectin antibody therapy were evaluated in a primate model of sepsis.

Methods

Sixteen baboons were anesthetized and randomized into two groups. The experimental group received 2 mg/kg of the anti-L-selectin antibody HuDREG-55 and the control group received Ringer's solution prior to the onset of a 2 h infusion of Escherichia coli (1–2 × 10⁹ colony forming units (CFU)/kg body weight). Serial blood samples were drawn over a 72 h period for the measurement of tumour necrosis factor-α, IL-6 and polymorphonuclear elastase. In addition, blood gas analysis, hematology and routine clinical chemistry were determined to monitor cardiovascular status, tissue perfusion and organ function.

Results

The three-day mortality rate and the mean survival time after E. coli-induced sepsis were similar in the two groups. The bacterial blood CFU levels were significantly higher in the placebo group than in the anti-L-selectin group. Other parameters measured throughout the 72 h experimental period, including the cardiovascular, immunologic, and hematologic responses as well as indicators of organ function and tissue perfusion, were similar in the two groups, with the exception of serum creatinine and mean arterial pressure at 32 h after E. coli challenge.

Conclusion

Anti-L-selectin therapy did not adversely affect survival, promote organ dysfunction or result in major side effects in the baboon sepsis model. Additionally, as anti-L-selectin therapy improved the bacterial clearance rate, it appears that this therapy is not detrimental during sepsis. This is in contrast to previous studies using the baboon model, in which antibody therapy used to block CD18 increased mortality.