Cannabinoids and alcohol co-exposure modulate pathogen-induced pulmonary immune responses

Area of Science:

• Immunology
• Pharmacology
• Pulmonology

Background:

• Alcohol and cannabinoid misuse are significant public health issues.
• Cannabinoid receptors (CBRs) role in pulmonary inflammation is not well understood.
• Cannabis is frequently used with alcohol, prompting investigation into combined effects.

Purpose of the Study:

• Investigate binge cannabinoid exposure effects on pathogen-induced pulmonary inflammation.
• Develop an adolescent binge ethanol + cannabinoid mouse model for studying lung inflammation.
• Elucidate the role of CBRs in pulmonary immune activation during polysubstance use.

Main Methods:

• Established an adolescent mouse model involving binge ethanol and cannabinoid exposure followed by *Klebsiella pneumoniae* infection.
• Administered cannabinoid antagonists to assess their impact on inflammation.
• Measured pulmonary immune activation and danger-associated molecular pattern (DAMP) release.

Main Results:

• Adolescent cannabinoid exposure primes lungs for exacerbated inflammation in adulthood.
• Cannabinoid antagonists mitigated the heightened inflammatory response.
• Ethanol and cannabinoid pre-exposure led to CBR-dependent pulmonary immune activation via DAMP release.

Conclusions:

• Adolescent cannabinoid exposure has long-term consequences on pulmonary inflammation.
• CBR signaling is implicated in the pulmonary immune response to microbial challenge and polysubstance use.
• Findings offer a framework for developing therapeutics for polysubstance use disorders affecting lung health.