Infectious Complications of Acute Pancreatitis Is Associated with Peripheral Blood Phagocyte Functional Exhaustion.

BACKGROUND: Infected pancreatic necrosis is one of the most severe complications of acute pancreatitis (AP). The development of secondary infection doubles the risk of death during the late stage of necrotizing pancreatitis. Phagocytes play a major role in AP pathogenesis, as well as in local and systemic complications of the disease. AIMS: We aimed to investigate the relationship between quantitative and functional indices of circulating phagocyte at the time of admission and onset of infectious complications in patients with AP afterward. METHODS: A post hoc analysis of 97 patients with AP was conducted. The metabolic state of peripheral blood neutrophils and monocytes was analyzed based on their phagocytic activity and generation of reactive oxygen species (ROS), which were determined by flow cytometry on admission. The clinical end point was marked by onset of infectious complications of AP. RESULTS: On admission, baseline values and reactivity reserve of monocyte and neutrophil phagocytic activity in AP patients, who developed septic complications, were substantially decreased, whereas monocyte ROS generation was dramatically increased as compared to the group without infectious processes. ROC curve was obtained both for neutrophil and monocyte phagocytosis reactivity reserve expressed as modulation coefficient values and categorized as the risk factor of infectious complications, showing an area under curve of 0.95 (P < 0.0001) and 0.84 (P < 0.0001), respectively. CONCLUSIONS: Early (at the time of admission) detection of quantitative and functional indices of circulating phagocytes can be useful for the prediction of septic complications in SAP patients.

Immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells.

PURPOSE: Tumor cell resistance to platinum-based chemotherapeutic agents is one of the major hurdles to successful cancer treatment with these drugs, and is associated with alterations in tumor cell immune evasion and immunomodulatory properties. Immunocyte targeting is considered as a relevant approach to fight drug-resistant cancer. In this study, immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells (LLC/R9) were investigated. METHODS: Immunological features of LLC/R9 cells cultured in vitro in normoxic and hypoxic conditions as well as of those that were grown in vivo were examined. The expression of immunologically relevant genes was evaluated by RT-PCR. Tumor cell susceptibility to the macrophage contact tumoricidal activity and NK-mediated cytolysis was investigated in MTT test. TNF-α-mediated tumor cell apoptosis as well as macrophage phagocytosis, oxidative metabolism, and CD206 expression after the treatment with conditioned media from normoxic and hypoxic tumor cells were studied by flow cytometry. Flow cytometry was also used to characterize dendritic cell maturity. RESULTS: When growing in vitro, LLC/R9 were characterized by slightly increased immunosuppressive cytokine gene expression. Transition to in vivo growth was associated with the enhancement of transcription of these genes in tumor cells. LLC/R9 cells had lowered sensitivity to contact-dependent macrophage-mediated cytotoxicity and to the TNFα-mediated apoptosis in vitro. Conditioned media from hypoxic LLC/R9 cells stimulated reactive oxygen species generation and CD206 expression in non-sensitized macrophages. Acquisition of drug resistance by LLC/R9 cells was associated with their increased sensitivity to NK-cell-mediated cytolysis. Meanwhile, the treatment of LLCR/9-bearing animals with generated ex vivo and loaded with LLC/R9 cell-lysate dendritic cells (DCs) resulted in profoundly enhanced tumor metastasizing. CONCLUSION: Decreased sensitivity to macrophage cytolysis, polarizing effect on DCs maturation along with increased susceptibility to NK-cell cytotoxic action promote extensive local growth of chemoresistant LLC/R9 tumors in vivo, but hamper their metastasizing.