Suppression of humoral immunity in dogs by 15-deoxyspergualin.

Nemoto, Kyuichi; Ito, Junpei; Abe, Fuminori; Nakamura, Teruya; Takeuchi, Tomio; Umezawa, Hamao

doi:10.7164/antibiotics.40.1065

Cited by 21 publications

(6 citation statements)

References 5 publications

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“…The severity of leucopenia seems to be proportional to the dose and duration of treatment and may be caused by a cytostatic effect on haematopoietic stem cells, where the proliferation and differentiation of immature bone marrow cells is suppressed [26,27]. The reduction in B-cell fraction seen in our patients is particularly interesting since it is in accordance with previous reports showing inhibitory effects on antibody responses in mice [4,6,18,25] and dogs [23]. Although this study provides no information on antibody production, it indicates that human B cells are also affected.…”

Section: Discussionsupporting

confidence: 90%

15-Deoxyspergualin treatment of graft rejection in man: effect on mononuclear cells

Borg¹,

Ohlman²

1992

Transplant Int

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We studied the effects of 15-deoxyspergualin (DSG) on human mononuclear cells in blood when DSG was administered as anti-rejection treatment to kidney-transplant patients in combination with methylprednisolone (MP) in a safety study. The numbers of leucocytes, lymphocytes and monocytes, the percentages of T and B cells and the expression of the interleukin 2 receptor and the human leucocyte antigen DR locus (HLA-DR) were determined in blood from these patients and from patients treated with MP only. We found that the number of lymphocytes and monocytes decreased in all groups, as also did the CD4/CD8 ratio and the HLA-DR expression on monocytes. DSG counteracted the increase in the number of leucocytes observed in patients treated with MP only. Different effects of DSG and MP were also observed on B cells. While the percentage of CD20+ cells increased in the MP group, it remained unaltered in patients given low-dose DSG and/or was decreased in those given higher doses. Since available evidence suggests an effect of DSG on B-cell reactivity, this drug may become an important addition to the arsenal of immunosuppressive drugs in clinical transplantation.

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Section: Discussionsupporting

confidence: 90%

15-Deoxyspergualin treatment of graft rejection in man: effect on mononuclear cells

Borg¹,

Ohlman²

1992

Transplant Int

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“…They reported that while DSG was highly effective in inhibiting the primary immunoresponse and the development of memory, it was less effective in inhibiting an established immunoresponse. In other experimental studies, DSG has been shown to inhibit antibody responses [15,17,25]. When DSG was given to recipients after heart transplantation, it successfully suppressed the proliferation of B cells (sensitization inter-val 2 weeks) and class I1 antigen-positive cells (sensitization interval 6 months), resulting in prolonged allograft survival.…”

Section: Discussionmentioning

confidence: 99%

Sensitization interval and administration method alter the effect of 15-deoxy-spergualin on heart transplantation in sensitized recipient rats

et al. 1996

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We evaluated the effect of 15-deoxyspergualin (DSG) on accelerated rejection. Brown Norway rats (BN) served as organ donors and Lewis rats (LEW) as recipients. In an accelerated rejection model, after a LEW rat was sensitized with BN skin, a BN heart was transplanted. Various intervals between sensitization and heart transplantation were examined. The heart allografts in sensitized recipients were rejected earlier than those in unmodified recipients regardless of the sensitization interval. DSG (2.5 mg/kg per day), given to the recipients during the sensitization phase, significantly prolonged graft survival compared with the untreated hosts when the sensitization interval was short. When the recipients were treated with DSG after heart transplantation, heart graft survival was significantly prolonged regardless of the sensitization interval. Flow cytometric analysis and complement-dependent cytotoxicity tests revealed that DSG suppressed antidonor antibody formation and the postoperative administration of DSG significantly decreased the proliferation of B cells when the sensitization interval was short and the proliferation of class II antigen-positive cells when the sensitization interval was long.

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“…The influence of DSG on the immune system reportedly involves suppression of the mixed lymphocyte reaction (MLR), 9 action on cytotoxic T lymphocytes, 10 antibody formation by B cells, 11 and sparing of suppressor cells. 12 However, the immunological effect of this drug on activated T lymphocytes is not clear and is still controversial.…”

Section: Introductionmentioning

confidence: 99%

Influence of 15-deoxyspergualin on activated lymphocytes: Comparison of heart and renal rat transplantation models

Ueda

Itoh

Azuma

et al. 1999

Clinical and Experimental Nephrology

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Background. Among the immunological effects of 15-deoxyspergualin (DSG), its action on activated T lymphocytes with the interleukin 2 receptor (IL-2R) is controversial. Materials and methods. To investigate this action, we used rat heart and rat renal transplantation models in which Brown Norway rats (BN) served as the organ donors and Lewis rats (LEW) as the organ recipients. DSG was administered intraperitoneally to the recipients immediately after the operation. The percentage of IL-2R-positive cells and of CD4-and CD8-positive cells in the recipient spleen or allograft was evaluated. Results. The average survival period (days) of the BN heart or renal allograft in hosts treated with DSG was significantly longer than that in the untreated hosts. In the heart transplantation model, DSG decreased the percentage of IL-2R-positive cells and increased the CD4/CD8 ratio in the allograft. By contrast, in the renal transplantation model, DSG suppressed the percentage of IL-2R-positive cells in the spleen,but influenced neither the percentage of IL-2R-positive cells nor the CD4/CD8 ratio in the allograft. Conclusion. DSG extended allograft survival significantly in both heart and renal transplantation models. However, the influence of DSG on IL-2R-positive cells may be different in the two types of allografts.

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Suppression of humoral immunity in dogs by 15-deoxyspergualin.

Cited by 21 publications

References 5 publications

15-Deoxyspergualin treatment of graft rejection in man: effect on mononuclear cells

15-Deoxyspergualin treatment of graft rejection in man: effect on mononuclear cells

Sensitization interval and administration method alter the effect of 15-deoxy-spergualin on heart transplantation in sensitized recipient rats

Influence of 15-deoxyspergualin on activated lymphocytes: Comparison of heart and renal rat transplantation models

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