Spinal Cord Injury Enhances Lung Inflammation and Exacerbates Immune Response After Acute Lung Injury

Area of Science:

• Neuroscience
• Immunology
• Pulmonary Medicine

Background:

• Spinal cord injury (SCI) severity impacts pulmonary function, particularly with higher injury levels.
• Pathological lung mechanisms post-SCI are not fully understood, with prior research linking sympathetic dysfunction to lung issues in high thoracic SCI.
• This study explores if low-level SCI increases acute lung injury susceptibility via systemic inflammation independent of the sympathetic nervous system.

Purpose of the Study:

• To investigate the impact of low-level T9 contusion SCI on acute lung injury.
• To determine if SCI elicits systemic inflammatory responses affecting the lungs independently of sympathetic regulation.
• To analyze lung inflammation and immune cell infiltration following lipopolysaccharide (LPS) exposure in SCI mice.

Main Methods:

• Mice underwent T9 contusion spinal cord injury (SCI) or sham procedure.
• Mice were exposed to aerosolized lipopolysaccharide (LPS) to induce lung inflammation.
• Lung tissues and bronchoalveolar lavage (BAL) fluid were analyzed 24 hours post-LPS exposure for gene expression, cytokine levels, and immune cell infiltration.
• Bone-marrow-derived macrophages (BMDMs) from SCI and control mice were tested for LPS responsiveness.

Main Results:

• SCI mice showed significantly increased proinflammatory gene expression (SAA3, IRG1, NLRP3, IL-1beta, MCP-1) and cytokine release (IL-1beta, IL-6, MCP-1) in lungs post-LPS exposure compared to controls.
• Higher infiltration of neutrophils (Ly6G/C positive) and macrophages was observed in the lungs of SCI mice.
• Bone-marrow-derived macrophages (BMDMs) from SCI mice exhibited hyper-responsiveness to LPS.
• Spleen size and weight were not affected by T9 SCI, indicating no spleen atrophy.

Conclusions:

• Low-level T9 SCI enhances lung inflammation and immune responses following LPS challenge.
• Systemic inflammation post-SCI significantly influences organ-specific responses, particularly in the lungs.
• The observed lung inflammation appears to be independent of sympathetic nervous system disruption and spleen atrophy.