Dialyzable leukocyte extract differentially regulates the production of TNFalpha, IL-6, and IL-8 in bacterial component-activated leukocytes and endothelial cells.
Ojeda MO, van't Veer C, Fernández Ortega CB, Araña Rosainz Mde J, Buurman WA.
Division of Physical Chemistry, Center for Genetic Engineering and Biotechnology (CIGB), P.O. Box 6162, Havana, 10600, Cuba. miriam.ojeda@cigb.edu.cu
OBJECTIVE: To investigate i) whether the Dialyzable Leukocyte Extract (DLE) modulates the production of proinflammatory cytokines in leukocytes activated by the bacterial cell wall components lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN); ii) the effect of DLE on LPS-stimulated endothelial cells; and iii) whether the regulatory effect of DLE on inflammatory mediators is related to the modulation of Toll-like receptors (TLRs), NF-kappaB and cAMP signaling pathways. METHODS: Leukocytes were stimulated with LPS, LTA, and PGN in the presence of DLE. Endothelial cells were stimulated with LPS and treated with DLE. The levels of Tumor Necrosis Factor-alpha(TNFalpha), Interleukin-6 (IL-6), and IL-8 in culture supernatants were evaluated by ELISA. The expression of Toll-like receptor 2 (TLR2) and 4 (TLR4), NF-kappaB activity and cAMP levels were evaluated by flow cytometry, EMSA, and EIA, respectively. RESULTS: The addition of DLE to leukocytes stimulated with cell wall constituents suppressed the production of TNFalpha. However, DLE induced IL-8 release in monocytes and enhanced IL-6 and IL-8 production by activated monocytes and endothelial cells. Also, DLE induced TLR2 and TLR4 expression, and increased cAMP levels, whereas NF-kappaB activity was inhibited. CONCLUSIONS: The present data indicate the differential regulation by DLE of the production of TNFalpha, IL-6, and IL-8 cytokines, associated with effects on TLR2 and TLR4 expression and NF-kappaB and cAMP activities. We suggest a putative mechanism for the biological effects of DLE in activated leukocytes and endothelial cells.
PMID: 15750714 [PubMed - indexed for MEDLINE]
Cytotherapy. 2007;9(4):379-85.
Bovine dialyzable leukocyte extract modulates cytokines and nitric oxide production in lipopolysaccharide-stimulated human blood cells.
Franco-Molina MA, Mendoza-Gamboa E, Castillo-Tello P, Isaza-Brando CE, García ME, Castillo-León L, Tamez-Guerra RS, Rodríguez-Padilla C.
Departamento de Inmunología y Virología, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
BACKGROUND: In the current study, we determined whether bovine dialyzable leukocyte extract (bDLE) modulates lipopolysaccharide (LPS)-induced nitric oxide and cytokine overproduction. METHODS: Human whole blood cells were treated with LPS (50 ng) + bDLE (1 U). RESULTS: The bDLE treatment decreased nitric oxide as well as TNF-alpha, IL-6 and IL-10 (P <0.01) cytokine production. In addition, it decreased TNF-alpha, IL-1beta and IL-6 mRNA expression and suppressed IL-10 and IL-12p40 mRNA expression, but did not modulate IL-8 mRNA expression in LPS-stimulated human blood cells. DISCUSSION: Our results suggest that bDLE may effectively modulate the fatal symptoms of hypotensive shock associated with endotoxin (LPS)-induced nitric oxide and cytokine production, and this may offer therapeutic potential for the treatment of endotoxic shock.
PMID: 17573613 [PubMed - indexed for MEDLINE]
J Med Food. 2005 Spring;8(1):20-6.
Bovine dialyzable leukocyte extract modulates the nitric oxide and pro-inflammatory cytokine production in lipopolysaccharide-stimulated murine peritoneal macrophages in vitro.
Franco-Molina MA, Mendoza-Gamboa E, Castillo-León L, Tamez-Guerra RS, Rodríguez-Padilla C.
Departamento de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México. moyfranco@hotmail.com
Lipopolysaccharides (LPS) released from Gram-negative bacteria after infection initiate an exagerated response that leads to a cascade of pathophysiological events termed sepsis. Monocytes or macrophages produce many of the mediators found in septic patients. Targeting of these mediators, especially tumor necrosis factor (TNF)-alpha and nitric oxide (NO), has been pursued as a mean of reducing mortality in sepsis. Bovine dialyzable leukocyte extract (bDLE) is a dialysate of a heterogeneous mixture of low-molecular-weight substances released from disintegrated leukocytes of the blood or tissue lymphoid. In this study, to determine whether bDLE modulates NO and pro-inflammatory cytokine production, murine peritoneal macrophages were treated with bDLE (0.05 or 0.5 U/mL) before LPS (20 mg/mL) stimulation, and also LPS-stimulated murine peritoneal macrophages were treated with bDLE (0.05 or 0.5 U/mL) at 0, 4, 8, 12, and 24 hours. The bDLE significantly decreased NO production, and also decreased TNF-alpha and interleukin (IL)-6 but increased IL-10 production in LPS-stimulated murine peritoneal macrophages. Our results demonstrate that bDLE plays an important role in modulating TNF-alpha, IL-6, and NO production through IL-10, and this may offer therapeutic potential in clinical endotoxic shock.
PMID: 15857204 [PubMed - indexed for MEDLINE]
Biotherapy. 1996;9(1-3):55-9.Links
Profiles of cytokine production in recipients of transfer factors.
Alvarez-Thull L, Kirkpatrick CH.
Innovative Therapeutics, Inc., Denver, CO, USA.
Transfer factors are proteins that transfer the ability to express cell-mediated immunity from immune donors to non-immune recipients. The mechanisms of these effects have not been defined. The experiments described in this report were undertaken to test the hypothesis that a mechanism through which the beneficial effects of transfer factors are expressed in clinical situation is through "education" of the immune system to produce certain cytokines in response to antigenic stimulation. BALB/c mice were sensitized to Herpes simplexvirus (HSV) either by sublethal systemic or cutaneous infections by administration of a HSV-specific transfer factors. One week later their spleen cells were collected and single cell suspensions were stimulated in vitro with irradiated HSV or concanavalin. A Culture supernatants were collected and assayed for content of IL-2, IL-4, IL-10 and IFN-g. Spleen cells from infected mice responded to concanavalin A and to HSV by secreting large amounts of IL-2 and IFN-g, modest amounts of IL-10, and no IL-4. Transfer factor recipients produced similar cytokine profiles in response to concavalin A. These mice, however, responded to HSV by secreting IFN-g, but no IL-2. Thus, transfer factors treatment selectively affects cytokine production in response to antigenic stimulation.
PMID: 8993758 [PubMed - indexed for MEDLINE]