Lipopolysaccharide (LPS) is a bacterial component that activates intracellular signaling pathways upon binding to the Toll-like receptor (TLR)-4/MD-2 complex. It is well known that LPS injected into animals and high-dose (100 ng/mL to 1 μg/mL) LPS treatment to innate immune cells induce an inflammatory response. In contrast, LPS is naturally present in the gastrointestinal tract, respiratory tract, and skin of humans and animals, and it has been shown that TLR-4-deficient animals cannot maintain their immune balance and gut homeostasis. LPS from commensal bacteria can help maintain homeostasis against mucosal stimulation in healthy individuals. Oral LPS administration has been shown to be effective in preventing allergic and lifestyle-related diseases. However, this effect was not observed after treatment with LPS at high doses. In mice, oral LPS administration resulted in the detection of LPS at a low concentration in the peritoneal fluid. Therefore, LPS administered at low and high doses have different effects. Moreover, the results of in vitro experiments using low-dose LPS may reflect the effects of oral LPS administration. This review summarizes the utility of in vitro models using cells stimulated with LPS at low concentrations (50 pg/mL to 50 ng/mL) in elucidating the mechanisms of oral LPS administration. Low-dose LPS administration has been demonstrated to suppress the upregulation of proinflammatory cytokines and promote wound healing, suggesting that LPS is a potential agent that can be used for the treatment and prevention of lifestyle-related diseases.

Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 β, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.