Effects of FR-91 on immune cells from healthy individuals and from patients with non-Hodgkin lymphoma.

The immune system is subject to destruction and dysfunction as a result of attacks by pathogenic and environmental agents. In addition, many clinical situations exist in which it is desirable to stimulate or suppress the immune system. The present study evaluated the screening efficacy of flow cytometric lymphocyte subset typing in peripheral blood mononuclear cells from healthy individuals (HI) and from patients with non-Hodgkin lymphoma (NHL) treated with different concentrations of FR-91, a standardized lysate of microbial cells belonging to the Bacillus genus, and in vitro cytokine production. Increased expression of subset markers (CD3, CD4, CD8) in NHL and CD3 in HI suggests an immunomodulating effect of FR-91. In addition the results of cytokine production also demonstrated a clear effect of FR-91 on both populations. A significant increase of IL-6, IL-12, IFN-gamma and TNF-alpha was observed in the HI group after treatment with FR-91. In a similar manner an increase of IL-2, IL-6, IL-12, IFN-gamma and TNF-alpha was also observed in the NHL group. In conclusion FR-91 seems to affect lymphocyte subpopulations, in vitro cytokine production, as well as mitogen-induced lymphocyte activation in a dose-dependent manner in both healthy individuals and NHL patients.

Effects of fish-derived lipoprotein extracts on activation markers, Fas expression and apoptosis in peripheral blood lymphocytes.

Several factors may influence numbers and function of peripheral blood lymphocytes (PBLs) by different processes. We conducted this study to evaluate the effect of E-CAB-94011 and E-JUR-94013, two marine fish extracts from S. scombrus and T. trachurus, respectively, on in vitro PBLs activation and on the expression and functionality of Fas, a cell surface molecule that plays a central role in immune homeostasis and cytotoxic activity. PBLs from 24 healthy volunteers were isolated and flow cytometry was performed to measure the state of activation, Fas expression and apoptosis of PBLs. Functionality of Fas was tested by assessing apoptosis after incubation of isolated lymphocytes with agonistic anti-Fas antibodies in blood samples treated with both E-CAB-94011 and E-JUR-94013. Studies on the lymphocyte cell marker suggest a clear immune activation as measured by the increased levels of CD25, CD8, CD38, CD19 and HLA-DR in vitro expression on lymphocytes treated with both extracts. In addition, a significant reduction in the percentages of apoptotic CD19(+)CD38(+) double positive lymphocytes could be demonstrated in the treated samples with respect to controls (p<0.05). Therefore the present results indicate that both E-CAB-94011 and E-JUR-94013 in vitro are powerful immunoregulatory, increasing immune surveillance.

Association between APOE epsilon4 allele and increased expression of CD95 on T cells from patients with Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by progressive impairment of cognitive functions. AD has a strong and complex genetic etiology, and multiple genes, acting independently and/or interacting, likely to influence the risk of developing AD. To test whether the expression of Fas receptor is upregulated in peripheral blood T lymphocytes and whether or not it correlates with APOE genotypes, 88 patients with AD and 24 normal individuals as controls were included in this study. T lymphocytes from patients as opposed to controls did undergo DNA fragmentation after in vitro exposure to IgM anti-Fas. In addition, several activation markers (CD25, HLA-DR, and CD45R0) were increased after 72 h in culture with respect to the controls, and Fas expression was also significantly different from the control group (p < 0.01). Reverse transcription PCR for Fas mRNA yielded the same results. T cells from both patients and controls showed upregulation of Fas receptor expression after in vitro anti-CD3 stimulation. Co-culture experiments with interleukin-4 downmodulated surface Fas receptor expression on T cells from patients and at a lesser extent in the control group. AD patients with the APOE allele 4 showed an increased expression of CD95 (53% +/- 6) with respect to APOE allele 3 (38% +/- 4). The control group showed a 22% +/- 3 (allele 4) and 31% +/- 5 (allele 3), respectively. Hyperexpression of Fas mRNA and surface Fas receptor on CD45RO(+) T lymphocytes may explain the occurrence of inflammatory cellular infiltrates in the CNS of AD patients.