Cardiac transplantation graft rejection

Muromonab is a mouse monoclonal antibody against the CD3 receptor of T-lymphocytes. Its activity is based on inhibition of interactions between antigen-presenting cells and T-cells. By preventing antigen presentation it suppresses T-cell activation and proliferation. The indication for muromonab is the treatment of acute graft rejection after kidney, liver and hart transplantations. Its adverse effects consist of those symptoms that are initiated by the release of cytokines and lymphokines as a result of the reaction of muromonab with CD3 positive T-lymphocytes. These symptoms may vary from a mild flu-like syndrome to serious cardiac, pulmonale and neurological reactions. 

It is a cyclic polypeptide with 11 amino acids. It selectively inhibits T-lymphocytes proliferation, IL-2 and other cytokine production. It is the most effective drug for prevention and treatment of graft rejection reaction. It is used in cardiac, hepatic, renal, bone marrow transplantation and as second line drug in rheumatoid arthritis, inflammatory bowel disease, dermato-myositis, bronchial asthma and certain other autoimmune diseases. 

Indication Prophylaxis of graft rejection in patients receiving renal and cardiac allogeneic transplantation... 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

Bishop DK, Shelby J, Eichwald EJ. 1992. Mobilization of T lymphocytes following cardiac transplantation. Evidence that CD4- positive cells are required for cytotoxic T lymphocyte activation, inflammatory endothelial development, graft infiltration and acute allograft rejection. Transplantation. 53 849-857. 

Suppression of organ graft rejection. Mouse to rat cardiac transplantation was performed. One group of rats was exposed to 400 ppm CO in air for 2 days following the operation and survived for 50 days. The other group breathed air, and survived only 5-7 days [16]. 

Influenza infection has been a significant problem in cardiac transplant patients immunization of such patients could therefore be beneficial. However, its use has been limited by concern that stimulation of the immune system might in principle cause an increased risk of cardiac rejection. In the renal transplant experience, influenza infection itself can trigger an immunological response to cause graft rejection, as well as predisposing to other infections. Another concern is whether an immunosuppressed cardiac transplant recipient could seroconvert sufficiently. In a case-control study in 18 cardiac transplant recipients and 18 control patients 6 months or more beyond transplant surgery, there were no differences in the incidence of cardiac rejection or immune responses (28). 

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