Method for reducing or preventing systemic inflammation
Inventors
Herz, Udo • McMahon, Robert J. • Russell, William Michael • Neu, Josef
Assignees
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Publication Number
US-9408819-B2
Publication Date
2016-08-09
Expiration Date
Abstract
The present disclosure is directed to a novel nutritional formula for treating or preventing systemic inflammation in a subject. The nutritional formula comprises a therapeutically effective amount of inactivated Lactobacillus rhamnosus GG (LGG).
Core Innovation
The invention relates to a method for treating, preventing, or reducing systemic inflammation in a subject, including an infant experiencing intestinal inflammation and optionally hepatic inflammation and systemic inflammation. The method administers a nutritional formulation comprising inactivated Lactobacillus rhamnosus GG (LGG) as an inactivated LGG nutritional composition.
The invention is directed to therapeutic effectiveness associated with administering inactivated LGG cell equivalents per kg body weight per day, including between about 1×10^4 and about 1×10^10 cells per kg body weight per day. The disclosure contrasts the risk context for viable probiotics in preterm or immunosuppressed infants and provides that inactivated LGG is used instead.
The invention further links administration of inactivated LGG to reduced pro-inflammatory cytokine and chemokine release and to inhibition of NF-κB signaling, including preventing IkB ubiquitination and reducing NF-κB translocation. The disclosure includes experimental results in a rat pup-in-the-cup model and intestinal epithelial cells showing reduced systemic markers after LPS challenge and reduced IL-8 and NF-κB activation with inactivated LGG or UV-inactivated LGG.
Claims Coverage
The independent claims cover three related inventive concepts: (i) reducing systemic release of one or more pro-inflammatory cytokines in an infant with intestinal inflammation by administering a nutritional composition with a defined dose of inactivated Lactobacillus rhamnosus GG; (ii) reducing systemic release of one or more pro-inflammatory cytokines in an infant with hepatic inflammation with the same defined inactivated LGG dose; and (iii) preventing NF-κB translocation in an infant with systemic inflammation using the same defined inactivated LGG dose. Across the independent claims, the inventive features center on the specific use of inactivated LGG in an infant nutritional composition with defined cell-equivalent dosing.
Dose-defined inactivated Lactobacillus rhamnosus GG for reducing systemic cytokine release in intestinal inflammation
Administering to the infant a nutritional composition formulated to provide between about 1×10^4 and about 1×10^10 cells of inactivated Lactobacillus rhamnosus GG per kg body weight per day, to reduce the systemic release of one or more pro-inflammatory cytokines in an infant experiencing intestinal inflammation.
Dose-defined inactivated Lactobacillus rhamnosus GG for reducing systemic cytokine release in hepatic inflammation
Administering to the infant a nutritional composition formulated to provide between about 1×10^4 and 1×10^10 cells of inactivated Lactobacillus rhamnosus GG per kg body weight per day, to reduce the systemic release of one or more pro-inflammatory cytokines in an infant experiencing hepatic inflammation.
Dose-defined inactivated Lactobacillus rhamnosus GG for preventing NF-κB translocation in systemic inflammation
Administering to an infant a nutritional composition formulated to provide between about 1×10^4 and 1×10^10 cells of inactivated Lactobacillus rhamnosus GG per kg body weight per day, to prevent the translocation of nuclear factor-kappa B (Nkβ) in an infant experiencing systemic inflammation.
Across the independent claims, the core inventive coverage is the administration of a nutritional composition containing inactivated Lactobacillus rhamnosus GG at a specified cells-per-kg-per-day range to reduce systemic pro-inflammatory cytokine release in intestinal or hepatic inflammation and to prevent NF-κB (Nkβ) translocation in systemic inflammation.
Stated Advantages
Reduced systemic release of one or more pro-inflammatory cytokines in an infant experiencing intestinal inflammation.
Reduced systemic release of one or more pro-inflammatory cytokines in an infant experiencing hepatic inflammation.
Prevention of nuclear factor-kappa B (Nkβ) translocation in an infant experiencing systemic inflammation.
Documented Applications
Treat, prevent, or reduce systemic inflammation in a subject, including infants experiencing intestinal inflammation and optionally hepatic inflammation.
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