Featured Research

from universities, journals, and other organizations

Medical enigma: The healing element is also the enemy

Date:
April 3, 2013
Source:
The Hebrew University of Jerusalem
Summary:
The same factor in our immune system that is instrumental in enabling us to fight off severe and dangerous inflammatory ailments is also a player in doing the opposite at a later stage, causing the suppression of our immune response. Why and how this happens and what can be done to mediate this process for the benefit of humankind is the subject of a new article.

The same factor in our immune system that is instrumental in enabling us to fight off severe and dangerous inflammatory ailments is also a player in doing the opposite at a later stage, causing the suppression of our immune response.

Why and how this happens and what can be done to mediate this process for the benefit of humankind is the subject of an article published online in the journal Immunity by Ph.D. student Moshe Sade-Feldman and Prof. Michal Baniyash of the Lautenberg Center for General and Tumor Immunology at the Institute for Medical Research Israel-Canada at the Hebrew University Faculty of Medicine.

Chronic inflammation poses a major global health problem and is common to different pathologies -- such as autoimmune diseases (diabetes, rheumatoid arthritis, lupus and Crohn's), chronic inflammatory disorders, chronic infections (HIV, leprosy, leishmaniasis) and cancer. Cumulative data indicate that at a certain stage of each of these diseases, the immune system becomes suppressed and results in disease progression.

In their previous work, the Hebrew University researchers had shown that in the course of chronic inflammation, unique immune system cells with suppressive features termed myeloid derived suppressor cells (MDSCs) are generated in the bone marrow and migrate into the body's organs and blood, imposing a general immune suppression.

A complex network of inflammatory compounds persistently secreted by the body's normal or cancerous cells support MDSC accumulation, activation and suppressive functions. One of these compounds is tumor necrosis factor-a (TNF-a), which under acute immune responses (short episodes), displays beneficial effects in the initiation of immune responses directed against invading pathogens and tumor cells.

However, TNF-a also displays harmful features under chronic responses, as described in pathologies such as rheumatoid arthritis, psoriasis, type II diabetes, Crohn's disease and cancer, leading to complications and disease progression. Therefore, today several FDA- approved TNF-a blocking reagents are used in the clinic for the treatment of such pathologies.

What has remained unclear until now, however, is just how TNF-a plays its deleterious role in manipulating the host's immune system towards the generation of a suppressive environment.

In their work, the Hebrew University researchers discovered the mechanisms underlying the TNF-a function, a key to controlling this factor and manipulating it, perhaps, for the benefit of humans. Using experimental mouse models, they showed unequivocally how TNF-a is critical in the induction of immune suppression generated during chronic inflammation. The TNF-a was seen to directly affect the accumulation and suppressive function of MDSCs, leading to an impaired host's immune responses as reflected by the inability to respond against invading pathogens or against developing tumors.

Further, the direct role of how TNF-a works in humans was mimicked by injecting the FDA-approved anti-TNF-a drug, etanercept, into mice at the exacerbated stage of an inflammatory response, when MDSC accumulation was observed in the blood. The etanercept treatment changed the features of MDSCs and abolished their suppressive activity, leading to the restoration of the host's immune function.

Taken together, the results show clearly how the TNF-a-mediated inflammatory response, whether acute or chronic, will dictate its beneficial or harmful consequence on the immune system. While during acute inflammation TNF-a is vital for immediate immune defense against pathogens and clearance of tumor cells, during chronic inflammation -- under conditions where the host is unable to clear the pathogen or the tumor cells -- TNF-a is harmful due to the induction of immune suppression.

These results, providing new insight into the relationship between TNF-a and the development of an immune suppression during chronic inflammation, may aid in the generation of better therapeutic strategies against various pathologies when elevated TNF-a and MDSC levels are detected, as seen, for example, in tumor growths.


Story Source:

The above story is based on materials provided by The Hebrew University of Jerusalem. Note: Materials may be edited for content and length.


Journal Reference:

  1. Moshe Sade-Feldman, Julia Kanterman, Eliran Ish-Shalom, Mazal Elnekave, Elad Horwitz, Michal Baniyash. Tumor Necrosis Factor-α Blocks Differentiation and Enhances Suppressive Activity of Immature Myeloid Cells during Chronic Inflammation. Immunity, 2013; 38 (3): 541 DOI: 10.1016/j.immuni.2013.02.007

Cite This Page:

The Hebrew University of Jerusalem. "Medical enigma: The healing element is also the enemy." ScienceDaily. ScienceDaily, 3 April 2013. <www.sciencedaily.com/releases/2013/04/130403104216.htm>.
The Hebrew University of Jerusalem. (2013, April 3). Medical enigma: The healing element is also the enemy. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2013/04/130403104216.htm
The Hebrew University of Jerusalem. "Medical enigma: The healing element is also the enemy." ScienceDaily. www.sciencedaily.com/releases/2013/04/130403104216.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins