Brain endocannabinoids modulate lung Inflammation during sepsis (1157.4)

Sepsis is a systemic inflammatory response caused by infection which can lead to shock and lung injury. Previous studies indicate that septic shock is mediated by brain endocannabinoid 1 (CB1) receptors. Hence, this study tested the hypothesis that the brain CB1 receptors regulate LPS-induced lung inflammation. Male Sprague-Dawley rats received an intracerebroventricular (ICV) injection of either the CB1 receptor antagonist Rimonabant (2 µg/kg) or vehicle, 5 minutes prior to IV injection of either LPS (5 mg/kg) or saline. Lungs were removed 0.5 h or 4 h after IV injection of LPS and isolated for assessment of pulmonary capillary pressure (Ppc), lung wet/dry weight ratio (W/D), TLR4 activation, α7nicotinic acetylcholine (α7nAch) pathway, IL-6 and VCAM. LPS- 0.5 h induced a decrease in lung levels of IRAK1 and IκBα indicating activation of TLR4, and decreased phosphorylated Src-Y416 family kinases (pSFK) and phosphorylated Raf1-S259 (pRaf1) suggesting decreased α7nAch signaling all which were prevented by R...