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. DESIGN: Prospective, randomized animal study. SETTING: Experimental laboratory. SUBJECTS: Male Sprague-Dawley rats, 200-240 g. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.
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. DESIGN: Prospective, randomized animal study. SETTING: Experimental laboratory. SUBJECTS: Male Sprague-Dawley rats, 200-240 g. INTERVENTIONS: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 CLPrats +/- sophorolipid treatment (three per group) were analyzed for cytokine production by RNase protection assay. MEASUREMENTS AND MAIN 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.
Authors: Alexis M Ziemba; Manoj K Gottipati; Filbert Totsingan; Cheryl M Hanes; Richard A Gross; Michelle R Lennartz; Ryan J Gilbert Journal: ACS Chem Neurosci Date: 2017-02-07 Impact factor: 4.418
Authors: Helen L Lydon; Niki Baccile; Breedge Callaghan; Roger Marchant; Christopher A Mitchell; Ibrahim M Banat Journal: Antimicrob Agents Chemother Date: 2017-04-24 Impact factor: 5.191
Authors: Breedge Callaghan; Helen Lydon; Sophie L K W Roelants; Inge N A Van Bogaert; Roger Marchant; Ibrahim M Banat; Christopher A Mitchell Journal: PLoS One Date: 2016-06-06 Impact factor: 3.240
Authors: Sib Sankar Giri; Hyoun Joong Kim; Sang Guen Kim; Sang Wha Kim; Jun Kwon; Sung Bin Lee; Se Chang Park Journal: Int J Mol Sci Date: 2020-09-23 Impact factor: 5.923