Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways.

Excessive production of cytokines by microglia may cause cognitive dysfunction and long‐lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti‐inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide‐ (LPS‐) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS‐treated mice and LPS‐treated BV‐2 microglial cells. In the TSA‐pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS‐induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3‐dioxygenase (IDO), TNF‐α, MCP‐1, and IL‐1β in the brain of LPS‐challenged mice and in the LPS‐treated BV‐2 microglial cells was lower. TSA diminished LPS‐induced inflammatory responses in the mouse brain and modulated the cytokine‐associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression.

Obesity and its associated complications are global public health concerns. Metabolic disturbances and immune dysregulation cause adipose tissue stress and dysfunction in obese individuals. Immune cell accumulation in the adipose microenvironment is the main cause of insulin resistance and metabolic dysfunction. Infiltrated immune cells, adipocytes, and stromal cells are all involved in the production of proinflammatory cytokines and chemokines in adipose tissues and affect systemic homeostasis. Interferons (IFNs) are a large family of pleiotropic cytokines that play a pivotal role in host antiviral defenses. IFNs are critical immune modulators in response to pathogens, dead cells, and several inflammation-mediated diseases. Several studies have indicated that IFNs are involved in the pathogenesis of obesity. In this review, we discuss the roles of IFN family cytokines in the development of obesity-induced inflammation and insulin resistance.

Lipopolysaccharide (LPS) may activate hypoxia-inducible factor (HIF)-1α, which up-regulates cytokine expression and the lethality of LPS-induced shock. We investigated the effect of propofol on HIF-1α expression and acute lung injury in LPS-treated mice. A series of both positive and negative control experiments were performed. We injected BALB/C mice with propofol or vehicle i.p. immediately and 12 h after an LPS challenge. After 24 h, we examined the lung wet/dry weight ratio, neutrophil infiltration, and HIF-1α mRNA expression and inflammatory cytokines in the lung tissue. Survival was determined for 48 h after LPS injection. In vitro, we determined the responses of A549 cells, with and without HIF-1α silenced, to treatment with LPS alone and LPS plus propofol. Propofol prolonged survival and attenuated acute lung injury and decreased the expression of HIF-1α, interleukin (IL)-6, keratinocyte-derived chemokine, and tumour necrosis factor-alpha (TNF-α) in the lungs of endotoxaemic mice. In HIF-1α knockdown-A549 cells, LPS-induced TNF-α, IL-6, and the pro-apoptotic gene, BNIP3 expression and apoptosis were reduced. Propofol, but not an inhibitor of nuclear factor κB, reduced HIF-1α expression in LPS-stimulated A549 cells. Propofol also down-regulated, in A549 cells, the expression of IL-6, IL-8, and TNF-α, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), and apoptosis. Propofol reduces apoptosis in LPS-stimulated lung epithelial cells by decreasing HIF-1α, BNIP3, and cytokine production. Using propofol to inhibit HIF-1α expression may protect against the acute lung injury caused by LPS-induced sepsis.