Zhang and colleagues explored the immunomodulatory activity of the cholesterol-lowering agent simvastatin. Their pharmaco-dynamic studies indicated that the immuno-modulatory activity of statins may involve two basic mechanisms. First, it may involve an increase in SOCS-3 and SOCS -7, i.e. members of the molecular family of “Suppressors of Cytokine Secretion”. And second, it may involve the inhibition of Interleukin-17 (IL-17), a central pro-inflammatory mediator.
The members of the SOCS family of molecules are important negative feedback regulators in adaptive and innate immune responses, while IL-17 producing CD4+ cells, the so-called “Th17 cells”, play a central role in the development of autoimmune diseases.
From their findings the authors conclude as follows: “Based on the described immunomodulatory mechanisms, good safety profile and oral biovailabalility, statins represent a promising therapeutic approach for multiple sclerosis and other chronic inflammatory diseases.”
Along the lines of this study by Zhang and colleagues, FOCUS Immunology is prepared to provide state-of-the-art services for pharmacodynamic (PD) analyses of immuno-modulatory compounds under GLP conditions.
If you are interested in learning more or in discussing your specific experimental needs, please feel free to contact Dr. Eddy Bruyns, Head of FOCUS Immunology Laboratory via e-mail eddy.bruyns@focus-cdd.com or via telephone +49 6221 64935124.
Source
Zhang et al.
Simvastatin Inhibits IL-17 Secretion by Targeting Multiple IL-17-Regulatory Cytokines and by Inhibiting the Expression of IL-17 Transcription Factor RORC in CD4+ Lymphocytes
The Journal of Immunology 2008; 180; 6988-6996
Suppressors of Cytokine Signaling (SOCS) are a group of proteins that play an important role in attenuating immune responses. These molecules may thus be important players in the pharmacodynamics (PD) of immuno-modulatory therapies.
In a recent publication Lee and colleagues explored whether probiotics induced anti-inflammatory properties through induction of SOCS.
Helicobacter pylori (H. pylori) or lipopolysaccharides derived thereof were found to increase the expression of pro-inflammatory cytokines in a human gastric cell line. Pre-treatment of the cells with probiotic bacteria of the Lactobacillus group reduced the H.Pylori-induced expression of these cytokines.
When the underlying molecular mechanisms were explored in more detail, the administration of probiotics was found to increase the expression of SOCS-2 and SOCS-3.
The authors conclude that the “Anti-inflammatory signals of SOCS … might be a key anti-inflammatory mechanism of probiotics …”
FOCUS Immunology is prepared to provide state-of-the-art servcies for pharmacodynamic (PD) studies for immunomodulatory compounds under GLP conditions.
If you are interested in learning more about FOCUS Immunology’s experience and offers or if you want to discuss your specific experimental needs, please feel free to contact Dr. Eddy Bruyns, Head of FOCUS Immunology Laboratory via e-mail eddy.bruyns@focus-cdd.com or via telephone +49 6221 64935124.
Source
Jeong Sang Lee et al.
Anti-inflammatory actions of probiotics through activating suppressor of cytokine signaling (SOCS) expression and signaling in Helicobacter pylori infection: A novel mechanism
Journal of Gastroenterology and Hepatology 25 (2010) 194-202
The myeloid/monocytic lineage of haematopoietic cells has an enormous functional and phenotypic plasticity.
Monocytes contained in circulating blood are an eminent example for this. After having entered peripheral tissues monocytes develop into tissue macrophages which play various roles under physiological and pathological conditions: removal of pathogens, antigen uptake and presentation, resolution of wound healing and propagation of chronic inflammations.
Moreover, cultured peripheral blood monocytes can be developed into professional antigen-presenting cells, so-called Dendritic Cells, which are used in tumor clinical vaccination protocols.
FOCUS Immunology has implemented state-of-the-art protocols for the in vitro maturation of functional active cell populations from human peripheral blood monocytes. In vitro generated cell populations, like Dendritic Cells or Macrophages are particularly suitable to explore specific aspects of immuno-modulatory and immuno-suppresssive compounds and treatment strategies.
For further information please contact us at immunology@focus-cdd.com or contact directly our Head of FOCUS Immunology Dr. Eddy Bruyns at eddy.bruyns@focus-cdd.com.
One of FOCUS Immunology’s key services is immune-monitoring in clinical trials.
In the presentation basic options of this service are outlined.
Please note that this is not a standard procedure, but that the actual procedures and parameters will be tailored to the specific needs of a given clinical trial.
FOCUS Immunology’s experts are looking forward to discuss this in detail with you.
Contact:
Dr. Eddy Bruyns, Ph.D.
Telephone: +49 6221 649 350
Email:eddy.bruyns@focus-cdd.com
Our basic test program for innate immunity testing quantifies the extent to which ligands specific for the nine known human Toll-like receptors (TLR) stimulate peripheral blood mononuclear cells (PBMC) isolated from individuals. The degree of stimulation is quantified via the amount of Tumor Necrosis Factor-alpha (TNF-alpha) secreted into the culture supernatants.
An example for a typical experiment is given here (click on the image to enlarge view):
PBMC were isolated from the blood of two human volunteers and cultured in the presence of distinct ligands for toll-like receptors (TLR-1 to -9). After a given interval of time the culture supernatants were harvested and tested for the amount of secreted TNF-alpha by enzyme-linked immunosorbent assay (ELISA).
The ligands and the corresponding TLRs are shown on the X-axis. The Y-axis provides the read-out parameter, i.e. amount of TNF-alpha in the culture supernatants. The left-most sample in both diagrams represents TNF-alpha secretion the unstimulated control culture.
Strongest responses were found for the TLR-4 ligand lipopolysaccharide (LPS) and the TLR 8 ligand single-stranded RNA (ssRNA40). The weak-responding TLR 3, 7 and 9 stimulations are again highlighted in the right hand diagram with a differently-scaled Y-axis in order to demonstrate the above-background response.
Please note, that this basic ex vivo assay design can be adapted to the specific requirements of a given project – be it for immune screening purposes in clinical trials or be it for mode-of-action or PD measurements in compound development.
Friday, July 2, 2010
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