Chemical and biological therapy
To date, drug-induced immunosuppression is considered the most promising method of affecting the adult organism during transplantation. The main goal of such therapy is to maximally suppress the activity of lymphoid tissue.
The arsenal of surgeons and immunologists includes the following groups of drugs:
- Chemical and biological agents.
- Hormonal preparations.
- Specific antibiotics (primarily actinomycins C and D).
Despite their efficacy, this approach has severe complications. The drugs exhibit extremely high toxicity to other organs and tissues. Due to a total decrease in the body's overall resistance, patients become defenseless against any infections (microbes and viruses). This dictates a strict requirement: patients must be kept in absolutely sterile conditions. Consequently, the search for new, more effective, but less toxic compounds is continuously underway.
Total body irradiation
The use of X-rays and gamma rays to reduce the reactivity of the immunocompetent system began to be actively studied in the 1950s during the earliest attempts at kidney transplantation. Animal experiments showed that irradiation reliably prolongs graft survival.
The clinical case involving Yugoslav physicists had a special impact on the development of this method. Following a nuclear reactor accident, they received lethal doses of radiation. French scientist G. Mathé took an unprecedented step—he performed a bone marrow transplant from healthy donors to the victims. The transplanted cells successfully engrafted. This phenomenon led researchers to consider the intentional use of artificial irradiation in safe doses to facilitate organ engraftment.
In practice, total body irradiation does prolong graft function, but it causes a severe complication: radiation sickness. Fatal outcomes are possible even at doses not exceeding 600 R.
Local and extracorporeal irradiation
Due to the colossal risks of total body exposure, radiological techniques have been modified into safer alternatives.
- Local irradiation. Only the transplanted organ itself and nearby lymph nodes are exposed. A prime example is the method of Japanese researcher I. Shikata. He proposed injecting radioactive gold directly into the lymphatic pathways. The isotope penetrates the lymph nodes and irradiates them from within. During the application of this method, favorable outcomes were achieved in 6 cases.
- Extracorporeal irradiation. This is the safest variant of radiation immunosuppression. The patient's lymph or blood is diverted outside the body through specialized tubes (shunts) and irradiated. The main mechanism of the method lies in the removal or inactivation of active lymphocytes circulating in the bloodstream. The key advantage is the complete absence of toxic radiation effects on the body as a whole.
Briefly: answers to topical questions
What specific hormonal drugs are prescribed in immunosuppressive therapy?
Sources designate glucocorticoids as hormonal immunosuppressants; the reference representative of this group is prednisolone.
Glucocorticoids are used to treat autoimmune diseases and prevent graft rejection. Their molecular mechanism of action includes:
- penetration through the cell membrane into the cell;
- binding to a specific intracellular cytosolic receptor;
- translocation of the hormone-receptor complex into the cell nucleus;
- interaction with gene promoters and regulation of DNA transcription.
The immunosuppressive effect is achieved through:
- inhibition of the transcription of genes encoding major histocompatibility complex (MHC) proteins;
- suppression of pro-inflammatory cytokine synthesis;
- inhibition of T-lymphocyte proliferation.
What chemical drugs (cytostatics) are used to prevent graft rejection?
First-generation chemical immunosuppressants used in immunology, especially in organ transplantation, include cytotoxic agents:
- mercaptopurine — the first drug used;
- azathioprine — a modification of mercaptopurine with the addition of an imidazole group to reduce high toxicity;
- cyclophosphamide.
Sources also mention antibiotics such as actinomycins C and D among drugs for immunosuppressive therapy.
Mechanism of action of first-generation chemical immunosuppressants: they are structural analogues of nitrogenous bases, interfere with the synthesis of nucleic acid precursors, disrupt DNA replication, and cause cell death during division.
Which isotopes are used for interstitial local irradiation of lymph nodes?
For local lymph node irradiation, sources specify the radioactive gold isotope.
I. Shikata's method: radioactive gold is injected into the lymphatic pathways; the isotope penetrates the lymph nodes and irradiates them. Favorable outcomes were obtained in 6 cases.
To memorize the types of irradiation, use the rule "TLE": T – Total (dangerous, causes radiation sickness), L – Local (targeted at the organ and nodes), E – Extracorporeal (safe, blood is irradiated via shunts outside the body).
Class and exam questions
What is the main goal of immunosuppressive therapy during transplantation?
The main objective is to suppress the activity of lymphoid tissue to reduce the reactivity of the immune system and prevent rejection of the transplanted organ.
What antibiotics are used as immunosuppressants?
In clinical practice, antibiotics of the actinomycin group, specifically actinomycins C and D, are used for these purposes.
What is the essence of the extracorporeal irradiation method?
Blood or lymph is diverted outward through specialized shunts, irradiated to inactivate active lymphocytes, and returned back. This eliminates the toxic effects of radiation on the entire body.
Why was widespread total body irradiation abandoned?
Despite prolonging graft survival, total body irradiation causes severe radiation sickness. Lethal outcomes have been recorded even at doses up to 600 R.
What else to study on this topic
- Mechanisms of action of actinomycins C and D on lymphoid tissue
- Specifics of keeping patients in sterile conditions during immunosuppression
- Clinical case of G. Mathé: the first successful bone marrow transplantation
- I. Shikata's technique: administration of radioactive gold into lymphatic pathways
- Technique of placing shunts for extracorporeal irradiation of blood and lymph
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