FGF8 Enhances Immunity and Protects Against Polymicrobial Sepsis
Overview
FGF8 levels increase in sepsis and enhance host immune defense by promoting macrophage bacterial clearance via ERK1/2 signaling. Therapeutic FGF8 administration improves survival and reduces bacterial burden in a mouse sepsis model, while FGF8 blockade worsens outcomes. Clinically, elevated serum FGF8 correlates with sepsis in adult and pediatric patients.
Background
Sepsis is a life-threatening syndrome caused by an unbalanced host response to infection, often leading to immunosuppression, organ failure, and death. Fibroblast growth factor 8 (FGF8) is known for roles in cell growth, survival, and immune regulation, but its function in sepsis was previously undefined. Understanding host factors like FGF8 that modulate immune responses may offer new diagnostic and therapeutic strategies for sepsis. This study investigates FGF8's role in polymicrobial sepsis using mouse models and clinical samples.
Data Highlights
Parameter
Findings
FGF8 protein levels in CLP-induced septic mice
Elevated compared to controls
Effect of anti-FGF8 antibody in septic mice
Increased mortality, bacterial burden, and tissue injury
Improved bacterial clearance and survival in FGFR1-dependent manner
FGF8 effect on macrophages in vitro
Enhanced bacterial phagocytosis and killing via ERK1/2 phosphorylation; effect blocked by ERK1/2 inhibitor U0126
Serum FGF8 levels in ICU patients with sepsis
Significantly higher than healthy controls in both adults and children
Key Findings
FGF8 protein concentrations are significantly elevated in septic mice induced by cecal ligation and puncture (CLP).
Blocking FGF8 with an antibody increases mortality, bacterial load, and tissue damage in septic mice.
Recombinant FGF8 administration enhances bacterial clearance and improves survival through FGFR1 receptor signaling.
FGF8 directly promotes macrophage bacterial phagocytosis and killing by activating the ERK1/2 signaling pathway; this effect is inhibited by ERK1/2 pathway blockade.
Serum FGF8 levels are significantly higher in adult and pediatric ICU patients with sepsis compared to healthy controls, suggesting diagnostic potential.
Clinical Implications
FGF8 represents a promising target for immunotherapy in sepsis by enhancing innate immune defense mechanisms, particularly macrophage function. Measuring serum FGF8 levels may aid in the early diagnosis and monitoring of sepsis in both adult and pediatric patients. Therapeutic strategies that augment FGF8 signaling could improve bacterial clearance and reduce mortality in septic patients.
Conclusion
FGF8 plays a critical protective role in sepsis by boosting host anti-infective immunity and improving survival outcomes. Targeting FGF8 pathways offers potential for novel diagnostic and therapeutic approaches in managing polymicrobial sepsis.
References
Original Article 2024 -- FGF8 Enhances Host Anti-Infective Immunity and Offers Protection Against Polymicrobial Sepsis
