Interleukin-1 Receptor Antagonists Partially Inhibited Histological Injury but Not Tissue Inflammation in a Sheep...

Area of Science:

• Reproductive biology
• Immunology
• Perinatal medicine

Background:

• Intrauterine inflammation is a major cause of preterm birth and fetal injury.
• Current interventions for intrauterine inflammation are limited.
• Interleukin-1 receptor antagonists (IL-1RA) are potential therapeutic agents.

Purpose of the Study:

• To investigate the efficacy of fetal intramuscular administration of IL-1 receptor antagonists (IL-1RA), anakinra and rytvela, in resolving intrauterine inflammation induced by lipopolysaccharides (LPS) in a pregnant sheep model.
• To assess the impact of IL-1RA treatment on fetal inflammatory markers, tissue injury, and brain development.

Main Methods:

• Pregnant Merino ewes were administered intraamniotic E. coli lipopolysaccharides (LPS) to induce inflammation.
• Fetuses received either saline, anakinra, or rytvela via intramuscular injection.
• Evaluated fetal outcomes included inflammatory mediator levels, immune cell infiltration, and markers of brain injury (microglial and oligodendrocyte staining).

Main Results:

• LPS exposure led to elevated fetal bilirubin, leukopenia, and increased inflammatory mediators in amniotic fluid and lung tissue.
• Both anakinra and rytvela treatments reduced immune cell infiltration in chorioamniotic membranes and lungs.
• While treatments reduced microglial staining and increased oligodendrocyte staining, they did not significantly resolve overall intrauterine inflammation compared to saline control.

Conclusions:

• Fetal intramuscular administration of anakinra and rytvela did not fully resolve LPS-induced intrauterine inflammation in the sheep model.
• IL-1RA treatments demonstrated potential in mitigating fetal tissue invasion and markers of brain injury.
• These findings suggest that even modest inflammation reduction may offer protective effects against brain injury and preterm birth, warranting further investigation into optimal therapeutic strategies.