Immune Response of Peripheral Blood Mononuclear Cells to Lipopolysaccharide in vitro in Patients with Primary Biliary Cirrhosis

  Objective  To explore the roles of lipopolysaccharide (LPS) and cytokines in the pathogenesis of primary biliary cirrhosis (PBC).

  Methods  The peripheral blood mononuclear cells (PBMCs) were collected from PBC patients, patients with primary Sjögren's syndrome (pSS), and healthy controls and then cultured in vitro in RPMI 1640 medium with or without LPS. The immune responses of PBMCs to 0.01mg/ml LPS in vitro were investigated by measuring the levels of cytokines(IL-1β, IL-2, IL-6, IL-10, TNF-α, IFN-γ) in supernates using enzyme-linked immunosorbent assay (ELISA).

  Results  The response of freshly extracted PBMCs to LPS were remarkably different from that of the resuscitated PBMCs. In the supernates of PBMCs cultured without LPS for 24 hours in vitro, the level of IL-2 was significantly higher in PBC patients than in healthy controls (P < 0.05). In the supernates of PBMCs cultured with 0.01mg/ml LPS for 24 hours in vitro, the levels of IL-1β, IL-2, and TNF-α were significantly higher in PBC patients than in healthy controls (P < 0.05). After the stimulation of LPS, the elevation rate of IL-1β and decrease rate of IL-2 in PBC patients were significantly higher than those in healthy controls (P < 0.05). Compared with the pSS patients, the levels of cytokines in PBC patients showed no difference in culture media without LPS, while IL-6 level was significantly increased in the supernates cultured with LPS in PBC patients. IFN-γ were seldomly detected in the the supernates of PBMCs from PBC patients, even after the LPS concentrations were increased to 0.1 and 1.0 mg/ml.

  Conclusions  The occurence of PBC is related to bacterial infections, in which LPS may play an important role. Many cytokines are involved in the pathogenesis of PBC, especially Th1 subtype.