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Language, Tone, and Volume of Glycoprotein Signals to Modulate Cytokines for Proper Immune Response

Comments by J. C. Spencer

The language, tone, and volume of glycoprotein signals hold the key to the future of medical science.  They hold the key to the ultimate diagnostic analysis.  Understanding these codes will enable us to better see the battlefield of hidden health challenges.  As we learn the language, tone, and volume of these signals can we better develop the strategies for winning the battles.  Every cell of the human body is transmitting signals in its cry for help or simply in its request for proper nutrition.

In this posting you will see that scientists are pushing the boundaries and peering into the possibilities for new diagnostic tools. Let us look at the research done here in the US on the IL-8 protein and then look at the work with the IL-8 work done in France for modulating cytokine response via glycoprotein coding on a virus and we gain new understanding of viral infections.

Scientists continue to verify the importance of the glycoproteins.  Their importance is conclusive and unchallenged.  Our intellectually understanding of the language of glycoproteins is not as important today as the cells understanding each other.  The cells understand the glycoprotein language, tone and they regulate the volume when there are enough healthy glycoprotein receptor sites to do so.

While waiting on all the coming diagnostic technology, let us invest our time and money eating the nutrients that are the building blocks for the glycoproteins.  Let us grow an abundance of glycoprotein receptor sites and we may discover that the coming diagonostic analysis will report good health.  Any skeptic of glycomics is welcome to participate in their own six month self-evaluation program through The Endowment for Medical Research from our website at www.endowmentmed.org/

Now, here is one article from the USA and one abstract from France:

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Science News

Immune System Protein Accurate Predictor Of Survival In Pediatric Septic Shock

ScienceDaily (Aug. 5, 2008) - - - About 4,000 children in the United States die every year from uncontrolled infections of the body known as septic shock, and researchers are pushing the boundaries of molecular science to find new therapies that can stem the condition. But a simple measure of an immune system protein within 24 hours of being admitted to the hospital for septic shock can predict survival in children, yielding a powerful tool for diagnostics and clinical trials of new septic shock therapies, according to a research team led by Cincinnati Children's Hospital Medical Center in the Aug. 1 American Journal of Respiratory and Critical Care Medicine.

The protein, interleukin-8 (IL-8), is secreted into the blood as part of the body's immune system response, the chief defense mechanism against infection-related conditions like septic shock. Previous research by the authors showed that higher blood levels of IL-8 are associated with more severe cases of pediatric septic shock and a greater chance of death. That research also pointed to the potential value of IL-8 as an early diagnostic marker of systemic bacterial infections.

The new study reports an IL-8 blood level at or below 220 pg/ml (picograms per milliliter) should allow doctors to predict with 95 percent accuracy which children with septic shock can survive through conventional antibiotics and therapies for at least 28 days following admission. Additionally, measuring IL-8 levels would make it possible to screen lower risk patients out of interventional clinical trials of experimental therapies, said Hector Wong, M.D., a physician and researcher of Critical Care Medicine at Cincinnati Children's and the study's lead author.

"Using IL-8 as a biomarker to screen low-risk septic shock patients from clinical trials of experimental or potentially high-risk therapies is an effective strategy to improve the risk-to-benefit ratio of a given intervention," said Dr. Wong, who also is professor of pediatrics at the University of Cincinnati College (UC) of Medicine. "Excluding patients who respond to standard care would enable investigators to focus clinical trial enrollment on patients least likely to respond well to conventional methods and find the most effective new therapies."

Because the reagents to measure IL-8 are available and blood samples can readily be obtained from patients, Dr. Wong wants to develop a "point-of-care" test that can be used to detect the Il-8 biomarker in septic shock patients, especially patients being considered for clinical trials. He has submitted a provisional patent application with the United States Patent and Trademark Office through the Cincinnati Children's Research Foundation for IL-8 as a stratification biomarker in pediatric septic shock.

Despite today's potent antibiotics and pediatric intensive care units, septic shock remains a serious public health challenge. Sepsis sets off a chain reaction of events that can ultimately lead to uncontrolled inflammation in the body and puts a person's entire immune system into overdrive.

When infections spread throughout the bloodstream, known as sepsis, the immune system makes certain proteins called cytokines, including IL-8 and other interferons, to help fight the infection. The presence of cytokines and toxins from the infection dilates blood vessels, dropping blood pressure to dangerously low levels. Blood flow to vital organs, including the kidneys and brain, becomes inadequate. The heart tries to compensate, but it weakens as blood vessels walls may leak, allowing fluid into tissues and the lungs, which can cause difficulty breathing. The resulting condition, in which multiple organs malfunction, is called septic shock.

Apart from antibiotics, supportive care and vaccination strategies, no specific therapies are approved by the FDA for pediatric septic shock.

For their study, Dr. Wong and colleagues obtained blood serum measurements and other patient information from two separate databases that included a total of 332 septic shock patients younger than 10 years old. Using statistical analyses of IL-8 levels obtained within 24 hours of hospital admissions, the researchers projected that a threshold of 220 pg/ml blood serum would have sensitivity for predicting rates of deaths in patients 75 percent of the time. The subsequent analyses, conducted separately on patient data from both databases, revealed a much higher validation of 95 percent accuracy when using an IL-8 level of 220 pg/ml or less to predict septic shock survivability at 28 days following hospital admission.

One of the databases, the Genomics of Pediatric Septic Shock (GPSS) database, was developed by Cincinnati Children's and the UC College of Medicine with contributing data and analyses from 18 pediatric intensive care units across the United States. The other database, RESOLVE (Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective), includes data and analyses from 51 sites in the U.S., Australia, France, Chile, Italy, Mexico, Poland, Slovakia, Switzerland and the United Kingdom. RESOLVE was developed and provided by Eli Lilly Research Laboratories, Indianapolis, Ind.

Study participants included Cincinnati Children's, the UC College of Medicine, Children's Hospital and Research Center (division of Critical Care Medicine), Oakland, Calif,; and Eli Lilly Research Laboratories. Funding support came from the National Institutes of General Medical Sciences and the Cincinnati Children's Research Foundation.

Adapted from materials provided by Cincinnati Children's Hospital Medical Center, via EurekAlert!, a service of AAAS

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Titre du document / Document title

Co-injection of interleukin 8 with the glycoprotein gene from viral haemorrhagic septicemia virus (VHSV) modulates the cytokine response in rainbow trout (Oncorhynchus mykiss)

Auteur(s) / Author(s)

JIMENEZ N. (1) ; COLL J. (2) ; SALGUERO F. J. (1) ; TAFALLA C. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Centro de Investigación en Sanidad Animal (CISA-INIA), Carretera de Algete a El Casar km. 8,1, Valdeolmos 28130, Madrid, ESPAGNE
(2) SGIT, INIA, Biotecnología, Carretera de La Coruña km. 7, 28040 Madrid, ESPAGNE

Résumé / Abstract

Since previous results showed that interleukin 8 (IL-8) was induced in rainbow trout (Oncorhynchus mykiss) in response to viral hemorrhagic septicemia virus (VHSV) infection, we have cloned IL-8 in an expression vector (pIL8+) and studied its possible adjuvant effect on the early response to a VHSV immunization model, focusing on the early response of several cytokines induced by a vector coding for the glycoprotein of VHSV (pMCV1.4-G) in the spleen and head kidney. First, we demonstrated that the pIL8+ successfully transcribed IL-8, by induction of IL-8 transcription in the muscle and blood, and by a massive infiltration of neutrophils at the muscle inoculation site. We have studied the effect of pIL8+ co-administration on the expression of two pro-inflammatory cytokines, such as IL-1? and tumour necrosis factor a (TNF-a); cytokines that have mainly an inhibitory role, IL-11 and transforming growth factor p (TGF-p); and a Th1 type cytokine, IL-18. We demonstrated that the co-administration of pIL8+ with pMCV1.4-G modulates the cytokine response that is induced, mainly by having its effect increasing pro-inflammatory cytokines (IL-1? and TNF-a 1), with a greater impact on the spleen, and to a lesser extent in the head kidney. All these data suggest that IL-8 is able to modulate the early cytokine immune response that is produced in response to a DNA vaccine, and therefore, might be a potential immune adjuvant in fish viral vaccination. More work should be done to determine if this modulation has a beneficial effect on protection as seen in other mammal viral models.

Revue / Journal Title

Vaccine ISSN 0264-410X CODEN VACCDE

Source / Source

2006, vol. 24, no27-28, pp. 5615-5626 [12 page(s) (article)] (59 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Oxford, ROYAUME-UNI (1983) (Revue)

Mots-clés anglais / English Keywords

Salmonidae; Vertebrata; Pisces; Virus; Mononegavirales; Rhabdoviridae; Septicemia; Hemorrhage; Immunological adjuvant; Genetic vaccine; Cytokine; Gene; Glycoprotein; Interleukin 8; Oncorhynchus mykiss; Viral hemorrhagic septicemia virus;

Mots-clés français / French Keywords

Salmonidae; Vertebrata; Pisces; Virus; Mononegavirales; Rhabdoviridae; Septicémie; Hémorragie; Adjuvant immunologique; Vaccin génétique; Cytokine; Gène; Glycoprotéine; Interleukine 8; Oncorhynchus mykiss; Virus septicémie hémorragique virale;

Mots-clés espagnols / Spanish Keywords

Salmonidae; Vertebrata; Pisces; Virus; Mononegavirales; Rhabdoviridae; Septicemia; Hemorragia; Coadyuvante inmunológico; Vaccina genética; Citoquina; Gen; Glicoproteína; Interleuquina 8; Oncorhynchus mykiss; Viral hemorrhagic septicemia virus;

Mots-clés d'auteur / Author Keywords

Interleukin 8 (IL-8); Viral hemorrhagic septicaemia virus (VHSV); DNA vaccine; Adjuvant;

Localisation / Location

INIST-CNRS, Cote INIST : 20289, 35400011571727.0110

You may purchase the paper at http://cat.inist.fr/?#

Last Updated ( Aug 12, 2008 at 11:31 AM )