IL-1 receptor activation undermines respiratory motor plasticity after systemic inflammation

Area of Science:

• Neuroscience
• Respiratory Physiology
• Immunology

Background:

• Inflammation negatively impacts neural plasticity, particularly in the respiratory system.
• Interleukin-1 (IL-1) signaling is implicated in modulating plasticity in various central nervous system regions.

Purpose of the Study:

• To investigate if IL-1 receptor (IL-1R) activation is necessary to impair phrenic long-term facilitation (pLTF) following systemic inflammation.
• To determine if spinal IL-1β is sufficient to impair pLTF in healthy animals.

Main Methods:

• Lipopolysaccharide (LPS) was used to induce systemic inflammation in rats.
• Phrenic long-term facilitation (pLTF) was induced by acute intermittent hypoxia (AIH).
• Peripheral and spinal IL-1R antagonism (AF-12198) and direct spinal administration of recombinant rat IL-1β (rIL-1β) were employed.

Main Results:

• Systemic inflammation (LPS) significantly reduced pLTF, which was restored by peripheral IL-1R antagonism.
• Spinal IL-1R antagonism also restored pLTF in LPS-treated rats, confirming IL-1R's necessity.
• Spinal IL-1β administration alone did not abolish pLTF but induced dose-dependent phrenic amplitude facilitation in the absence of AIH.

Conclusions:

• IL-1R activation, both systemically and spinally, is necessary to undermine respiratory motor plasticity after LPS-induced inflammation.
• While IL-1 signaling plays a role, it is not sufficient to completely abolish respiratory plasticity.
• Understanding IL-1's role is crucial for developing therapies that leverage respiratory plasticity for ventilatory disorders.