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KMID : 0377619750290040399
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Korean Jungang Medical Journal
1975 Volume.29 No. 4 p.399 ~ p.407
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Effects of Administration of Immunosuppressive drug (Azathioprine) on Skin Allograt in Mouse
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Abstract
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In addition to the classic humoral immunity, increasing emphasis has been recently placed on the significance of cellular or cell-mediated immunity as the specific imm unological responses of the host in a number of microbial infections and transplanta ntation procedures. Cell-mediated immunity can be divided into two subdivisions, i. e. antimicrobial cellular immunity and anti-tissue cellular immunity (Pearsall and Weiser, 1970)and extensive reviews on antimicrobial cellular immunity have been made by others (Mackaness and Blanden, 1967; Turk, 1967; Dannenberg, 1968).
It thus appears that the immune barrier is the major remaining problem prevent ing successful skin allograft.
The loci of formation of these antibodies are thought to be in lymph-node, spleen and bone marrow, and the cell most closely related with the rejection phenomenon is the lymphocyte.
The antigen in the graft which elicits the immune reaction may be the DNA. or some substance closely associated with it in the cell nuclei.
Homografts will survive for prolonged periods under special circumstances, e.g., in patients with agammaglobulinemia, severe burns and uremia.
In animals, acquired tolerance and radiation chimerism also permit long homograft survival.
Therefore the treatment of animals with Azathioprine or radiation will also delay homograft rejection.
It thus customary, in prolonging the survival of homograft with a chemical agent, to give frequent doses of the agent over a prolonged period. Effective agents are generally toxic, and their use is attended by considerable mortality, in both laboratory animals and man., The immune response is not uniformly susceptible to inhibition by these agents throughout its course, nor is it uniformly active. It is likely, therefore, that the schedules of administration not closely adapted to this changing sensitivity and activity of the immune response may, on one hand, subject the recipient to unnecessary toxicity and, on the other, fail to attack the immune response sufficiently during its most vulnerable period.
Leukopenia after irradiation is a well-known phenomenon and has been used by some as a measure of the effectiveness of the irradiation. Gershon-Cohen and Hermel have explored the early peripheral blood changes as a diagnostic procedure in irradiation. Rat irradiated showed a marked lymphopenia within the first 4 hours in the higher dose ranges. A leukocytosis, due to heterphiles, accompanied the lymphopenia and lasted approximately 48 hours. The leukocytosis was followed by a marked leukopenia which persisted until death.
Recent workers have indicated that the resulting leukopenia after X-irradiation may be responsible for the bactermia that is found in a large percentage of the animals and which ultimately results in their death (L. Gonshery, R. Q. Martson and W. W. Smith, 1953).
Regeneration of bone marrow, spleen, and lymphoid tissues as well as recovery of peripheral blood cells and body weight occur much earlier than in untreated animals at even lower X-ray dosage.
Also the circulating erythrocytes are not sensitive to irradiation.
Based on the above factors, the studies were carried out in mouse system to establish the effect of Azathioprine and irradiation of whole body on the changing peripheral blood and skin allograft and the results are summarized as follows;
1) In Azathioprine-treated mice, the rapid decrease of leukocyte was noted at 4th or 5th day after 1st administration of Azathioprine and the leukocyte count slowly returned to normal by 15th day but continuously decreased in preoperative and postoperative treated group.
2) The mice with Azathioprine treatment showed a rapid lymphopenia by 3rd or 4th day after 1st administration of Azathioprine and the percentage of lymphocyte within preoperative-treated group rapidly returned to normal by 7th day but the change of the percentage of lymphocyte within preoperative and postoperative-treat ed group showed the increase in spite of the continuous administration of Azathioprine and slowly returned to normal by 17day.
3) Mice within 24 hours after radiation showed a rapid leukopenia and leukocyte count quickly returned to normal but lymphocyte and segneutrophil count was not correlated to the leukocyte count.
4) Erythrocyte count showed the slowly decreased in all experimental groups. 5) Treatment with irradiation significantly prolonged survival time of skin allograft but the group with treatment of Azathioprine showed slight prolongation of survival time of skin allograft.
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