Double-edged sword: a recent study from the Hebrew University of Jerusalem has discovered that the same factor in our immune system that fights off certain kinds of inflammatory conditions also causes our immune system to grow weaker as we get older. Now that the discovery was made, researchers are trying to find the cause for this role-reversal – with the hopes of one day controlling it.
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Such chronic inflammation is common in many severe health disorders, such as autoimmune diseases (diabetes, rheumatoid arthritis, lupus and Crohn’s), chronic inflammatory disorders, chronic infections (HIV, leprosy, leishmaniasis) and cancer. What all these conditions have in common is that at a certain stage, the immune system becomes suppressed and results in disease progression.
Previous research done at the university has shown that the cause for the suppression is a kind of cell, called MSDC, which travels from the bone marrow to the circulatory system and imposes a general suppression of the immune system.
A natural mechanism gone wrong
The problem is that sometimes the body needs to suppress its own immune system in order to heal itself from harmful conditions. Researchers focused on a compound called TNF-a, which displayed beneficial effects in the initiation of immune responses directed against invading pathogens and tumor cells, when dealing with short episodes.
However, when a condition became chronic and reoccurring, TNF-a started displaying harmful effects, actually causing complications and disease progression. Such a negative phenomenon is characteristic of diseases such as rheumatoid arthritis, psoriasis, type II diabetes, Crohn’s disease and cancer. For that reason, TNF-a blocking reagents are used for 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. The Hebrew University researchers were able to identify the mechanisms that influence the way TNF-a operates.
Hopes for future treatment
Using mice, researchers were able to influence TNF-a with anti-TNF-a drugs. The 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.
The results were published online in the journal Immunity by Ph.D. student Moshe Sade-Feldman and Professor 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.
Photo: Andres Rueda