Follistatin Does Not Influence the Course of Escherichia coli K1 Sepsis in a Mouse Model

Abstract

Follistatin (FS) is the binding protein of activin A and inhibits its actions. The activin/FS system participates in the fine tuning of the immune response, and concentrations of activin A and FS are elevated in serum of patients with sepsis. Intraperitoneal injection of FS markedly reduced mortality after lipopolysaccharide-induced inflammation in a mouse model. Here, we investigated whether FS also influences the disease course in a mouse model of sepsis induced by intraperitoneal injection of Escherichia coli K1, a gram-negative bacterium frequently causing septic bacterial infections. Intraperitoneal injection of 10 μg/mL FS 30 min before infection did not influence survival, weight, motor performance, or bacterial titers of the infected mice. Thus, we could not confirm the protective effect of FS observed during lipopolysaccharide-induced inflammation in our mouse model of E. coli sepsis. Although it is a promising therapeutic tool in chronic or acute inflammatory conditions not caused by virulent pathogens, FS does not seem to increase the resistance to bacterial infections.

Systemic Escherichia coli infection does not influence clinical symptoms and neurodegeneration in experimental autoimmune encephalomyelitis

“…Our results suggest that the effect of moderately severe adequately treated systemic infections by E. coli on MS is less pronounced than suspected. Given the lack of efficacy of clinical and experimental trials based on targets identified in LPS studies [12, 41], our data confirm the complexity of systemic infections with viable bacteria compared to LPS-induced inflammation and underline the necessity of adequate infection models for testing the role of systemic infection in the pathogenesis of MS.…”

“…Systemic treatment of animals with LPS has been shown to promote relapses [9] and to enhance neurodegeneration in experimental models of MS [10]. Although frequently used for this purpose in animal models, LPS-induced inflammation does not accurately mimic a systemic infection with viable bacteria [11, 12]. Only few studies in humans or animal models demonstrated an exacerbating effect of an acute infection with Gram-negative bacteria on the disease course of MS and EAE [13–15].…”

Rational Design and Evaluation of an Artificial Escherichia coli K1 Protein Vaccine Candidate Based on the Structure of OmpA

“…However, these E. coli K1 induced-meningitis models are not suitable for vaccine assessment because 2–3 weeks is required for active immunization. Thus, systematic infection models partially representing the pathogenic process of E. coli K1 infection (Dieelberg et al, 2012 ; McCarthy et al, 2015 ) were applied for the evaluation of OmpAVac vaccination. Future studies should focus on evaluating the protection conferred by OmpAVac-specific antibodies in animals with neonatal meningitis.…”

Intracerebral Infection with E. coli Impairs Spatial Learning and Induces Necrosis of Hippocampal Neurons in the Tg2576 Mouse Model of Alzheimer’s Disease

“…In most experimental studies in this field, lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria with strong immunostimulatory properties, was used to induce inflammation [21,22]. Although LPS-induced inflammation is a reliable and reproducible stimulus, it does not accurately imitate an infection with viable bacteria [23,24], and caution is necessary, when translating results obtained with this artificial stimulus to real infections in humans [21,25]. For the development of optimized treatment strategies, there is still need of an animal model in which a genuine acute bacterial infection with a common pathogen worsens clinical symptoms of a neurodegenerative disease [26].…”