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


METHODS
Prospective, randomized animal study.


METHODS
Experimental laboratory.


METHODS
Male Sprague-Dawley rats, 200-240 g.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Bluth
Martin H
MH
SUNY Downstate Medical Center, Department of Surgery, Brooklyn, NY 11203, USA. martin.bluth@downstate.edu
Kandil
Emad
E
Mueller
Catherine M
CM
Shah
Vishal
V
Lin
Yin-Yao
YY
Zhang
Hong
H
Dresner
Lisa
L
Lempert
Leonid
L
Nowakowski
Maja
M
Gross
Richard
R
Schulze
Robert
R
Zenilman
Michael E
ME
D000818:Animals; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006017:Glycolipids / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008026:Ligation; D008264:Macrophages / Q000166:cytology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D011336:Probability; D011677:Punctures; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D018805:Sepsis; D012772:Shock, Septic / Q000276:immunology* / Q000517:prevention & control*
D016207:Cytokines; D006017:Glycolipids; D009569:Nitric Oxide