Ethanol-Induced Alterations of T Cells and Cytokines after Surgery in a Murine Infection Model.

BACKGROUND: Interactions between alcohol, infection, and surgery and their effect on differentiation and functionality of T helper cells are not yet completely understood. We hypothesized that alcohol and surgery disturb differentiation of T helper cells and contribute to an impaired immune response. METHODS: Mice were treated with alcohol for two weeks. Saline treatment served as control. Clinical performance and weight were assessed. On day 14, a median laparotomy was performed and animals were challenged with Klebsiella pneumoniae intranasally. Bacterial load was determined in lungs and blood. T helper cell subpopulations and the released cytokines were assessed in lungs, spleens, and plasma. Key transcription factors of T cell differentiation were evaluated. RESULTS: Alcohol significantly impaired clinical appearance and body weight of animals with postsurgical infection (p < 0.05). Bacterial load was significantly higher after alcohol treatment (p < 0.05). T helper cell subsets and released cytokine levels were significantly altered in lung, but not in spleen. Expression of transcription factors of T helper cell lineage commitment did not translate into different counts of T helper cells. CONCLUSIONS: Alcohol and surgery lead to significant cellular and functional modulations of T helper cells during postsurgical infection. These effects may contribute to an impaired immune response after surgery.

Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.