Didemnin b–an immunosuppressive cyclic peptide that stimulates murine hemagglutinating antibody responses and induces leukocytosis in vivo

David W. Montgomery, Abbie Celniker, Charles F. Zukoski

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35 Scopus citations

Abstract

Didemnin B (DB) is a cyclic peptide with potent immunosuppressive activity in vitro and in the murine graft-versus-host-reaction (GVHR), the only measure of in vivo immunity tested in our prior studies. Because continued production of mature leukocytes by bone marrow and an intact antibody response are crucial to defense against infection in immunosuppressed patients, we have evaluated the effects of DB on these processes as well. Anti-sheep red blood cell (SRBC) hemagglutinating antibody (hAb) production was induced by i.p. injection of 5×107 SRBC in CB6F1, mice (5/group) treated with vehicle or DB once/day for six days. Serum was collected on day 7 and hAb titers measured by SRBC agglutination. Control antibody titers were 1/16, while animals receiving DB doses of 0.025, 0.05, 0.10, and 0.20 mg/kg/day yielded titers of 1/37, 1/74, 1/56, and 1/74, respectively. This stimulation of hAb production (4.6 × control) was confirmed by a second experiment. We then studied DB effects (0.1 mg/kg/day x 6 days) on serum hAb titers in separate groups of five mice at 7, 10, 15, and 20 days postimmunization. Control hAb titers were 1/110 on day 7, then dropped to 1/60 on days 10, 15, and 20. DB-treated animals had titers of 1/130 on day 7, and 1/170 on days 10–20. These data show hat DB treatment in vivo causes a persisting increase.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalTransplantation
Volume43
Issue number1
DOIs
StatePublished - Jan 1987

ASJC Scopus subject areas

  • Transplantation

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