scholarly journals Immunosuppressive activity of corticotrophin-releasing factor. Inhibition of interleukin-1 and interleukin-6 production by human mononuclear cells

1992 ◽  
Vol 281 (1) ◽  
pp. 251-254 ◽  
Author(s):  
P Hagan ◽  
S Poole ◽  
A F Bristow
Keyword(s):  
Mononuclear Cells ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Peripheral Circulation ◽  
Maternal Blood ◽  
Immunosuppressive Activity ◽  
Acth Secretion ◽  
Corticotrophin Releasing Factor ◽  
Human Mononuclear Cells ◽  
Maternal Immune System

Corticotrophin-releasing factor (CRF) from the hypothalamus stimulates corticotrophin (ACTH) secretion. Concentrations of CRF in the peripheral circulation are normally low, and increase during pregnancy due to CRF secretion by the placenta [Cunnah, Jessop, Besser & Rees (1987) J. Endocrinol. 113, 123-131], although CRF in maternal blood does not appear to stimulate the hypothalamo-pituitary-adrenal (HPA) axis [Potter, Behan, Fischer, Linton, Lowry & Vale (1991) Nature (London) 349, 423-426]. We have examined the possibility that the placental. CRF might contribute to the suppression of the maternal immune system, which is necessary to prevent rejection of the foetus, by studying endotoxin-evoked cytokine production by monocytes as a model for activation of the immune response. CRF inhibited endotoxin-evoked cytokine production from human mononuclear cells (MNCs), the fraction of peripheral blood containing monocytes. The effects of CRF were reversed by a specific CRF receptor antagonist, and were additive with glucocorticoid inhibition of cytokine secretion. Anti-interleukin-1 (IL-1) antisera inhibited endotoxin-evoked IL-6 production; however, the CRF effect was not additive, suggesting that CRF inhibition of IL-6 production may be secondary to CRF inhibition of IL-1. These results suggest a role for CRF as an immunosuppressant during pregnancy.

Interleukin‐1 (IL‐1) receptor blockade reduces endotoxin and Borrelia burgdorferi ‐stimulated IL‐8 synthesis in human mononuclear cells

1992 ◽  
Vol 6 (7) ◽  
pp. 2482-2486 ◽  
Author(s):  
Reuven Porat ◽  
Debra D. Poutsiaka ◽  
Laurie C. Miller ◽  
Eric V. Granowitz ◽  
Charles A. Dinarello
Keyword(s):  
Borrelia Burgdorferi ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Receptor Blockade ◽  
Human Mononuclear Cells

Cryopreservation enhances interleukin-1 production in human mononuclear cells

Cryobiology ◽  
1990 ◽  
Vol 27 (2) ◽  
pp. 137-142 ◽  
Author(s):  
M. Venkataraman ◽  
M.P. Westerman
Keyword(s):  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Human Mononuclear Cells

NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3175-3182 ◽  
Author(s):  
Mamoru Ito ◽  
Hidefumi Hiramatsu ◽  
Kimio Kobayashi ◽  
Kazutomo Suzue ◽  
Mariko Kawahata ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Cytokine Production ◽  
Nk Cell ◽  
Severe Combined Immunodeficiency ◽  
Cell Activity ◽  
Peripheral Circulation ◽  
Interferon Γ ◽  
Recipient Mouse ◽  
Peripheral Blood Mononuclear ◽  
Cd34 Cells

AbstractTo establish a more appropriate animal recipient for xenotransplantation, NOD/SCID/γcnull mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rγ (IL-2Rγ) allelic mutation (γcnull) were generated by 8 backcross matings of C57BL/6J-γcnull mice and NOD/Shi-scidmice. When human CD34+ cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi-scid mice treated with anti-asialo GM1 antibody or in the β2-microglobulin–deficient NOD/LtSz-scid (NOD/SCID/β2mnull) mice, which were as completely defective in NK cell activity as NOD/SCID/γcnull mice. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. In addition to the high engraftment rate, multilineage cell differentiation was also observed. Further, even 1 × 102 CD34+ cells could grow and differentiate in this strain. These results suggest that NOD/SCID/γcnull mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/γcnull mice, cytokine production of spleen cells stimulated with Listeria monocytogenesantigens was compared among these 3 strains of mice. The interferon-γ production from dendritic cells from the NOD/SCID/γcnull mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/γcnull mice.

Interleukin 1 Gene Cluster, Myocardial Infarction at Young Age and Inflammatory Response of Human Mononuclear Cells

2009 ◽  
Vol 38 (3-4) ◽  
pp. 203-219 ◽  
Author(s):  
Maria Carmela Latella ◽  
Monica de Gaetano ◽  
Augusto Di Castelnuovo ◽  
Emanuela Napoleone ◽  
Roberto Lorenzet ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Inflammatory Response ◽  
Gene Cluster ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Young Age ◽  
Human Mononuclear Cells

scholarly journals Tumor necrosis factor is the major monocyte product that increases complement receptor expression on mature human neutrophils

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 151-158 ◽  
Author(s):  
M Berger ◽  
EM Wetzler ◽  
RS Wallis
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Time Course ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Systemic Effect ◽  
Receptor Expression ◽  
Human Neutrophils ◽  
Human Mononuclear Cells ◽  
Necrosis Factor

Interleukin-1 (IL-1) and other monocyte products have several important effects on the systemic response to infection in addition to their roles in lymphocyte stimulation. The present studies were carried out to determine whether products of stimulated monocytes activated circulating neutrophils (PMN) to increase expression of receptors for C3b (CR1) and C3bi (CR3), which are necessary for optimal margination, migration, and phagocytosis. Supernatants of human mononuclear cells that had been stimulated with lipopolysaccharide (LPS) or purified protein derivative (PPD) contained both tumor necrosis factor (TNF) and IL-1 and increased CR1 and CR3 expression on isolated PMNs. Supernatants of unstimulated cultures, media alone, or LPS or PPD alone had little or no effect. Supernatant effects were detectable at 1:3,000 final dilution and appeared to have a characteristic slow time course. These supernatants also caused dose- and time-dependent secretion of PMN granular constituents, but maximal receptor expression was accompanied by secretion of less than 10% of the cells' content of lysozyme and less than 16% of the B12 binding protein. Immunoadsorption studies showed that the supernatant's activity could be removed by anti- TNF but not by anti-IL-1. Recombinant IL-1 had no effect on receptor expression, but recombinant TNF increased CR1 and CR3 expression with kinetics similar to the supernatants. These results thus indicate that TNF is the major monocyte product that increases CR1 and CR3 expression on mature blood neutrophils. This would result in increased margination and phagocytic activity and may be an important systemic effect that would help the host eradicate infection.

Immune response to reovirus (REO) in phase I study with chemotherapy in patients with KRAS mutant metastatic colorectal cancer (mCRC).

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 217-217 ◽  
Author(s):  
Ruwan Parakrama ◽  
Imran Chaudhary ◽  
Matthew C. Coffey ◽  
Sanjay Goel ◽  
Radhashree Maitra
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Cells ◽  
Mononuclear Cells ◽  
Phase 1 ◽  
Interleukin 1 ◽  
Peripheral Circulation ◽  
Strong Immune Response ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf

217 Background: Viruses are well known immune sensitizing agents. The therapeutic efficacy of oncolytic reovirus in combination with chemotherapy is underway in a phase 1 study of mCRC. This study evaluates the nature of immune response by determining the distribution of antigen presenting cells (APCs) and activated T lymphocytes along with the cytokine expression pattern in peripheral circulation. Methods: REO was administered as a 60-minute intravenous infusion for 5 consecutive days every 28 days, at a tissue culture infective dose (TCID50) of 3x106. Serum was collected pre- and post- REO on days 1, pre REO on days 2-5, and days 8, 15, 22, and 29. Peripheral blood mononuclear cells (PBMC) were isolated and stained with fluorophore labelled antibodies against CD4, CD8, CD56, CD70, and CD123. Stained cells were fixed and evaluated by flow cytometry. The expression profile of 25 cytokines in plasma was assessed (post PBMC isolation) on an EMD Millipore multiplex Luminex platform. Results: Patients mount a robust immune response with dendritic cell maturation at 48 hrs (p < 0.01) followed by activation of cytotoxic T (CD8+) cells at Day 8 (p < 0.01). Cytokine assay indicated upregulation of Interleukin 1 beta (IL-1β; p = 0.004), Granulocyte-macrophage colony-stimulating factor (GM-CSF; p = 0.05), the chemokine Macrophage Inflammatory Proteins (MIP-1β; p = 0.05) at day 15. Furthermore, consistent upregulation of inflammatory cytokine IL-6 was seen from days 3 through 8 (p < 0.05), and decrease in IL-8 at 72 hrs (p = 0.03) was observed. Conclusions: REO induces strong immune response in patients with mCRC. APCs are stimulated within 48 hrs and activated (CD8+ CD70+) T cells within 168 hrs. Cytokine profiling indicates stimulation for maturation of APCs, chemotactic induction for macrophages and activation of T cells as highlighted by release of IL-1β, GM-CSF and MIP-1β respectively. Sustained increased expression of IL-6 (triggering lymphocyte maturation) and downregulation of IL-8 (pro-angiogenic cytokine) is also observed. REO thus functions bimodally as an oncolytic agent causing lysis of tumor cells, and facilitator of immune-mediated recognition and destruction of tumor cells. Clinical trial information: NCT01274624.

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