Immunomodulatory effects of anesthetics in obese patients

Figure 1 Model of obesity-associated pulmonary inflammation. Lung immune cells and inflammation due to obesity. Leptin is implicated in inflammatory respiratory diseases as a neutrophil chemoattractant. The association between obesity and LPS-induced lung inflammation involves an increase in monocytes and lymphocytes, as well as in intracellular adhesion molecule (ICAM)-1 expression in alveolar macrophages, suggesting their polarization toward a pro-inflammatory M1 phenotype. Obesity impairs vascular homeostasis, facilitating increased susceptibility to inflammatory lung vascular diseases by affecting structural cells in the alveolar-capillary membrane. The lung endothelium of obese mice has been shown to express higher levels of leukocyte adhesion markers (E-selectin, ICAM-1, VCAM-1) and lower levels of junctional proteins (VE-cadherin and β-catenin). Adiponectin has anti-inflammatory properties, mainly by its effects on toll-like receptor (TLR) pathway-mediated NF-κB signaling, which regulates the shift from M1 to M2 macrophage polarization, and suppresses differentiation of M1 macrophages by downregulating the pro-inflammatory cytokines TNF-α, MCP-1, and IL-6. Adiponectin also promotes expression of the anti-inflammatory factor IL-10 in macrophages via cAMP-dependent mechanisms. TNF: Tumor necrosis factor; IL: Interleukin; LPS: Lipopolysaccharide.

Figure 2 Modulatory effects of anesthetic agents on lung immune cells. A: Inhaled anesthetics: Decreased neutrophil influx, synthesis, and expression of macrophage inflammatory protein (MIP)-2, IL-1β, and stress proteins heme oxygenase (HO-1) and heat shock protein (HSP-70). Reduction of pro-inflammatory cytokine release, inhibition of iNOS expression and activity by blockade of NF-κB activation in lung tissue, inhibition of proapoptotic procaspase protein expression, and maintenance of alveolar epithelial adherence by attenuating reduction of zona occludens 1 (ZO-1) levels; B: Intravenous anesthetic (propofol): Impairs neutrophil activity by inhibition of phosphorylation of the mitogen-activated protein kinases p44/42 MAPK signaling pathway and disrupts the downstream signaling pathway involving calcium, Akt, and ERK1/2, which decreases superoxide generation, elastase release, and chemotaxis.