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GTS-21 reduces microvascular permeability during experimental endotoxemia
Karsten Schmidt1, Sukanya Bhakdisongkhram1, Florian Uhle1
1Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Microvascular Research
|August 19, 2017
Summary
GTS-21, a novel therapeutic, effectively reduces microvascular permeability in sepsis by targeting the alpha7 nicotinic acetylcholine receptor (α7nAChR). This finding suggests GTS-21
Area of Science:
- Pharmacology
- Sepsis Research
- Inflammation Biology
Background:
- Sepsis leads to increased microvascular permeability and tissue edema, with no effective pharmacological treatments currently available.
- Cholinergic mediators, particularly via the alpha7 nicotinic acetylcholine receptor (α7nAChR), exhibit anti-inflammatory effects.
- GTS-21, a selective α7nAChR agonist, has demonstrated anti-inflammatory properties and a favorable safety profile in clinical trials, making it a potential therapeutic candidate for sepsis.
Purpose of the Study:
- To evaluate the therapeutic potential of GTS-21 in mitigating microvascular permeability and leukocyte adhesion during experimental endotoxemia.
- To investigate the effect of GTS-21 on sepsis-induced inflammatory responses.
Main Methods:
- Male Wistar rats were subjected to experimental endotoxemia induced by lipopolysaccharide (LPS).
- Intravital microscopy (IVM) was employed to assess macromolecular leakage and leukocyte adhesion in the rat mesentery.
- GTS-21 was administered at various time points relative to LPS challenge, and systemic TNF-α levels were measured.
Main Results:
- GTS-21 significantly reduced microvascular permeability when administered simultaneously with or 1 hour after LPS induction.
- No significant effects of GTS-21 were observed on leukocyte adhesion, venular wall shear rate, or TNF-α levels.
Conclusions:
- GTS-21 demonstrates a protective effect on microvascular barrier function in experimental endotoxemia.
- The anti-inflammatory efficacy and safety profile of GTS-21 suggest its potential clinical benefit for treating capillary leakage in sepsis therapy.
