In his presentation Dr. Greb, president and CEO of Focus Clinical Drug Development GmbH (Neuss, Germany), summarizes pertinent issues of early phase development of biologicals.
He points out that careful analysis of the molecular situation is required and that the relevant target structures and species need to be chosen in preclinical evaluation of the compounds activity.
You may wish to download Dr. Greb’s presentation for your personal use. To order a complimentary copy of Dr. Greb’s presentationon specific challenges in human pharmacology trials with biologicals enter your email address below and press the submit button:
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“FOCUS Immunology Laboratories Heidelberg” offer testing of biomarkers for immune cell functions tailored to the specific requirements of a given clinical trial.
For further information please contact Dr. Eddy Bruyns at eddy.bruyns@focus-cdd.com.
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
Hyperactivation of the immune system can lead to tissue destruction and auto-immunity. Therefore, the amplitude and duration of immune responses after antigenic and cytokine signaling are regulated in a feedback manner.
So-called “Suppressors of Cytokine Signaling (SOCS)” are important molecular players in this negative feedback regulation. 7 members of the SOCS molecular family have been described so-far. The SOCS family members 1 and 3 are of particular importance, since they are involved in adaptive and innate immune responses.
SOCS-1 and -3 are induced by LPS stimulation via the Toll-like Receptor-4 (TLR-4). While SOCS-1 directly targets the downstream signaling molecules of TLR4, SOCS-3 regulates the secondary effects of many LPS-induced cytokines. E.g. IL-1R signalling pathways are negatively regulated by SOCS-3.
In adaptive immune responses SOCS-1 and -3 play a role in the regulation of T cell activation, proliferation and diferentiation.
Recently, SOCS molecules were found to be central elements in the pharmacodynamics of the immuno-modulatory compound simvastatin and probiotic lactobacilli.
FOCUS Immunology is prepared to provide state-of-the-art services for pharmacodynamic (PD) studies for immunomodulatory compounds under GLP conditions. This includes studies on the regulation of intra- and extracellular mediators of inflammationand immunity.
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
Dimitriou et al.
Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins
Immunological reviews 2008, Vol. 224: 265-283
More information on SOCS1: Wikipedia on SOCS1
More information on SOCS3: Wikipedia on SOCS3
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
Friday, July 16, 2010
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