Immunosuppressive mediators show that thin rejection and injury can be avoided with drugs

Immune inflammatory mediators are essential in pathology, transplantation, and regenerative medicine, scientists report in the American Journal of Pathology

Controlling inflammation after organ, cell, or cigarette transplantation is essential for graft survival; however, it can be difficult. Chronic injuries resulting from a harmful rejection can be particularly troubling.

Now, a team of researchers from the Albert Einstein College of Medicine reports that neutralization of the cell signaling molecule, tumor necrosis factor (TNF), can prevent the proliferation of molecules and signs of injury after cell transplantation in The American Journal of Pathology, published by Elsevier.

“New perspectives on immunosuppressive mediators show that rejection and thin injury can be avoided with the available drugs,” explained research team leader Sanjeev Gupta, MD, Department of Medicine and Pathology, and Research Center ae Marion Bessin, Albert Einstein College of Medicine, Bronx, NY, USA.

“The ability to prevent and / or control muscle injury will improve graft survival for transplant therapy, prior use of cells and tissues for regenerative medicine, and provide insight for controlling thin joint injuries. associated with inflammation in other conditions. “

Organ transplants from unrelated or unfair donors to individuals provide a protective barrier against “foreign” material. The development of immunosuppressive drugs to inhibit lymphocyte responses has been successful in the short term, but harmful rejection and thin lesions over long periods of time due to unknown mechanisms and processes may lead to loss of transplanted organs.

To understand the factors that work in rejection of tension, the researchers at the Albert Einstein College of Medicine developed liver cell transfusion models in laboratory rats with or without immunity, using drugs usually given to humans.

The state of inflammation was studied using gene expression arrays to interrogate transmissible signals associated with different cell types.

The analysis was guided by recent advances in mapping gene expression differences and the networks affected by complex interactions using commercially available computer software. The software queries the scientific literature to suggest negative or positive relationships and reactions in genes.

The studies identified differences in the expression of 40–50 soluble networks. In particular, the activation of TNF, a major inflammatory mediator, and its cell receptors are evident, continuing in the long term.

Inhibition of TNF inhibited the activation of most other inflammatory signals, indicating that it is a “major modifier” for cytokines, chemokines, and receptors arising from tissue or intestinal systems. protect the body against foreign substances, eg, microbes, viruses, and malignant transplants. .

To further understand the role of TNF, the researchers neutralized it with the drug based etanercept or thalidomide to promote cell transfusion results along with normal immunity to tacrolimus and mycophenolate mofetil.

Computer mapping of gene expression showed that TNF inhibition significantly reduces the recruitment and activity of inflammatory cells. Other studies provided direct evidence that TNF inhibition led to better survival and proliferation of transfusion cells, regenerating the liver much more efficiently.

Lead author Fadi-Luc Jaber, PhD, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA said “I was amazed by the effectiveness of this anti – inflammatory device for liver regeneration. There are more ways to treat a liver condition. “

The ability to interpret these findings is encouraging because the additional inflammatory symptoms and genes offer further ways to detect the pathophysiology of organ rejection in individuals. This type of inflammatory intervention reduces muscle injury, promotes graft survival, and the survival of transplanted cells and engineered cigarettes, and helps promote organ regeneration. The preventive cascades prescribed through TNF also hold lessons for the epidemiology in other less sensitive settings, such as COVID-19. “

Sanjeev Gupta, MD, Department of Medicine and Pathology, Albert Einstein College of Medicine