Sophorolipids block lethal effects of septic shock in rats in a cecal ligation and puncture model of experimental sepsis

• Published in: Critical care medicine Vol. 34; no. 1; p. 188
• Main Authors: Bluth, Martin H, Kandil, Emad, Mueller, Catherine M, Shah, Vishal, Lin, Yin-Yao, Zhang, Hong, Dresner, Lisa, Lempert, Leonid, Nowakowski, Maja, Gross, Richard, Schulze, Robert, Zenilman, Michael E
• Format: Journal Article
• Language: English
• Published: United States 01.01.2006
• Subjects: Animals; Cecum - surgery; Cytokines - biosynthesis; Disease Models, Animal; Glycolipids - pharmacology; Infusions, Parenteral; Ligation; Macrophages - cytology; Male; Nitric Oxide - biosynthesis; Probability; Punctures; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Sensitivity and Specificity; Sepsis; Shock, Septic - immunology; Shock, Septic - prevention & control
• ISSN: 0090-3493
• DOI: 10.1097/01.CCM.0000196212.56885.50

Sophorolipids, a family of natural and easily chemoenzymatically modified microbial glycolipids, are promising modulators of the immune response. The potential of the therapeutic effect of sophorolipids was investigated in vivo in a rat model of sepsis and in vitro by analysis of nitric oxide and cytokine production. Prospective, randomized animal study. Experimental laboratory. Male Sprague-Dawley rats, 200-240 g. Intra-abdominal sepsis was induced in vivo in 166 rats via cecal ligation and puncture (CLP); 60 rats were used to characterize the model. The remaining rats were treated with sophorolipids or vehicle (dimethylsulfoxide [DMSO]/physiologic saline) by intravenous (iv) tail vein or intraperitoneal (IP) injection immediately post-CLP (25/group). Survival rates were compared at 36 hrs after surgery. In vitro, macrophages were cultured in lipopolysaccharide (LPS) +/- sophorolipid and assayed for nitric oxide (NO) production and gene expression profiles of inflammatory cytokines. In addition, splenic lymphocytes isolated from CLP rats +/- sophorolipid treatment (three per group) were analyzed for cytokine production by RNase protection assay. CLP with 16-gauge needles optimized sepsis induction and resultant mortality. Sophorolipid treatment improved rat survival by 34% (iv) and 14% (IP) in comparison with vehicle controls (p < .05 for iv treatment). Sophorolipids decreased LPS-induced macrophage NO production by 28% (p < .05). mRNA expression of interleukin (IL)-1beta was downregulated by 42.5 +/- 4.7% (p < .05) and transforming growth factor (TGF)-beta1 was upregulated by 11.7 +/- 1.5% (p < .05) in splenocytes obtained 6 hrs postsophorolipid treatment. LPS-treated macrophages cultured 36 hrs with sophorolipids showed increases in mRNA expression of IL-1alpha (51.7%), IL-1beta (31.3%), and IL-6 (66.8%) (p < .05). Administration of sophorolipids after induction of intra-abdominal sepsis significantly decreases mortality in this model. This may be mediated in part by decreased macrophage NO production and modulation of inflammatory responses.