Influence of Oxisuran, a Differential Inhibitor of Cell-Mediated Hypersensitivity, on Allograft Survival and Humoral Immunity

Fox, Alfred E.; Gawlak, Daniel; Ballantyne, Donald L.; Freedman, Henry H.

doi:10.1097/00007890-197304000-00007

Cited by 22 publications

(8 citation statements)

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“…The experimental immunosuppressive agent, oxisuran, was also shown to be selectively toxic for T cells in our cell culture system. This finding correlates with previous animal studies which demonstrate the selective cellular immunosuppressive effects of this drug, with sparing of humoral immune responses [21,42,43]. Human plasma levels of oxisuran have not been reported but, in our cell culture system, the toxic concentration of oxisuran was found to be high relative to the other drugs studied.…”

Section: Discussionsupporting

confidence: 91%

“…The drugs were chosen from a broad range of pharmacologic classes including alkylating agents, purine and pyrimidine analogues and folic acid analogues. All of these drugs have demonstrated suppressive effects on immune function in humans, animal models and/or in vitro systems of cellular and/or humoral immunity [15][16][17][18][19][20][21] and, with the exception of oxisuran, are all in current clinical usage. Although the mechanism of action of cytotoxicity has been established for certain of these study drugs, the question of why they also cause immune dysfunction has not been answered at the biochemical level.…”

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confidence: 99%

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Effect of immunosuppressive agents on human T and B lymphoblasts

Kazmers

Daddona

Dalke

et al. 1983

Biochemical Pharmacology

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We have studied the effects of various immunosuppressive drugs on the growth of human-derived T (MOLT-4) and B (MGL-8) lymphoblasts. In addition, we have examined whether the lymphotoxic effect of any of these drugs could be attributed to inhibition of either adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP). Results indicated that 1-beta-D-arabinofuranosylcytosine (Ara-C), methotrexate and chlorambucil were four to seven times more toxic for T than for B cells, while azathioprine, 6-thioguanine, 6-mercaptopurine, and 5-fluorouracil were highly toxic for both T and B cells. Cyclophosphamide and oxisuran were lymphotoxic only at concentrations exceeding 300 microM. Deoxyadenosine (50 microM), deoxyguanosine (10 microM) and deoxycoformycin (10 microM) failed to enhance T cell toxicity when individually combined with each drug. None of the drugs tested inhibited T or B lymphoblast ADA or PNP activity. With the exception of Ara-C, neither dATP nor dGTP accumulated in T lymphoblasts incubated in the presence of any of the drugs. We conclude that the cell culture system used in this investigation is useful for identifying lymphotoxic and T cell-specific immunosuppressive agents. However, none of the drugs studied appeared to function as an inhibitor of, or a competitive substrate for, either ADA or PNP.

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

Effect of immunosuppressive agents on human T and B lymphoblasts

Kazmers

Daddona

Dalke

et al. 1983

Biochemical Pharmacology

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“…Freedman let al ( 16) and Fox et al (17) have reported that oxisuran suppresses skingraft rejections in mice, rats, and dogs but has no effect on antibody production. It differs from established immunosuppressants (e.g., glucocorticoids, antimetabolites) , which are capable of suppressing both.…”

Section: Ige-like Antibody Responsesmentioning

confidence: 99%

Tilorone: Its Selective Effects on Humoral and Cell-Mediated Immunity

Megel

Raychaudhuri

Goldstein

et al. 1974

Experimental Biology and Medicine

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“…In this study, oxisuran had little or no apparent effect on T. pallidum multiplication. This finding is not entirely unexpected since evidence suggests that oxisuran preferentially suppresses cellmediated immunity (6)(7)(8). Although the mechanism of action of adrenal corticosteroids, including dexamethasone, is not completely understood, it appears that steroid therapy also suppresses the host's cellular immunity in experimental syphilis (16), and thus it might be expected that oxisuran would add little to the immunosuppression resulting from dexamethasone treatment.…”

Section: Discussionmentioning

confidence: 95%

“…In an unpublished study, Arko found that the development of syphilitic skin lesions in rabbits could be prevented by using systemic immunosuppressive drugs and by allowing sufficient time (at least 3 months) for a connective tissue capsule to form around the chamber before inoculation. In such rabbits temporary multiplication of T. pallidum occurred in subcutaneous chambers, the largest treponemal yields being obtained in rabbits treated with both oxisuran, a reported differential inhibitor of cell-mediated hypersensitivity (6)(7)(8), and dexametha-T. PALLIDUM SUBCUTANEOUS CHAMBER INFECTION sone. With respect to the subcutaneous chamber model in general, Arko has reported that rabbits provided a larger source of chamber fluid and serum for laboratory testing and that guinea pigs were susceptible to secondary infection with a variety of microorganisms, thus requiring more care and more meticulous surgical technique in the implantation and inoculation procedures (3).…”

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Treponema pallidum infection in subcutaneous polyethylene chambers in rabbits

Tight¹,

Perkins²

1976

Infect Immun

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Male New Zealand white rabbits with subcutaneous polyethylene chambers in place for at least 3 months were inoculated by one of the following three methods: (i) "intra-chamber" (IC) inoculation with "normal"chamber fluid; (ii) intratesticular inoculation with Treponema pallidum; or (iii) IC inoculation with T. pallidum. Rabbits given dexamethasone only, oxisuran only, both drugs, or no drug were observed serially after inoculation. T. pallidum survived and temporarily multiplied to significant numbers within subcutaneous chambers after IC inoculation in rabbits given dexamethasone. In rabbits not treated with dexamethasone, T. pallidum counts in chamber fluid decreased rapidly and remained at low levels for 30 days after IC inoculation. Oxisuran appeared to have little or no effect on T. pallidum multiplication. All rabbits studied had a nonreactive serum and chamber fluid serological test for syphilis before inoculation. All rabbits inoculated with T. pallidum eventually developed reactive serum and chamber fluid serological tests. The IC route of inoculation was associated with a delay in the development of serum serological reactivity and with earlier chamber fluid reactivity as compared with the intratesticular route of inoculation. An immediate but transient influx of polymorphonuclear leukocytes was associated with IC inoculation of T. pallidum. Chamber fluid total protein content declined very slightly in all groups of rabbits during the month after inoculations. Successful cultivation of T. pallidum in an in vivo setting suggests that this animal model may be useful in further studies ofthe biology of the organism and ofthe pathogenesis, immunology, and treatment of syphilis.

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Influence of Oxisuran, a Differential Inhibitor of Cell-Mediated Hypersensitivity, on Allograft Survival and Humoral Immunity

Cited by 22 publications

References 0 publications

Effect of immunosuppressive agents on human T and B lymphoblasts

Effect of immunosuppressive agents on human T and B lymphoblasts

Tilorone: Its Selective Effects on Humoral and Cell-Mediated Immunity

Treponema pallidum infection in subcutaneous polyethylene chambers in rabbits

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