The most common characteristic observed in numerous diseases like rheumatoid arthritis or psoriasis is chronic inflammation. Endotoxemia is an important factor in these conditions as it is triggered by prolonged exposure to lipopolysaccharide (LPS), leading to inflammation and immune dysregulation. Therapeutic peptides are promising options to treat these chronic diseases with inflammatory characteristics. However, the applicability of therapeutic peptides is limited due to their poor stability in the body, which is typically overcome by cost-intensive modifications. Living therapeutics are emerging as a more cost-effective strategy to tackle this limitation by engineering microbes to produce and deliver the peptides right where they are needed. We developed an in-vitro endotoxemia (and psoriatic) model to test living therapeutics secreting anti-inflammatory peptides: KCF-18, I6P7, α-MSH (secreted from a genetically modified lactic acid-free strain of Lactiplantibacillus plantarum (TF103)) on murine macrophages, characterized the dose-response effects of these peptides and performed multi-array cytokine analysis. The model revealed that this living therapeutic approach enhanced the effects of the peptides, requiring lower amounts to achieve anti-inflammatory effects. Notably, α-MSH secreted by TF103 L. plantarum achieved significant pathway suppression, comparable to or exceeding that of synthetic controls, without inducing cytotoxicity. This points to potential synergistic effects between the peptides and the intrinsic anti-inflammatory properties of lactic acid bacteria. We will expand the applicability potential of these anti-inflammatory living therapeutic materials in an in vitro model of psoriasis.
Journal of Investigative Dermatology , 2025, 145 (11), Supplement, e35.