You are here
Discodermolide-a new, marine-derived immunosuppressive compound. II.In vivo studies
| Title: | Discodermolide-a new, marine-derived immunosuppressive compound. II.In vivo studies. |
 67 views 18 downloads |
|---|---|---|
| Name(s): |
Longley, Ross E. Caddigan, D. Harmody, Dedra K. Gunasekera, M. Gunasekera, Sarath P. Harbor Branch Oceanographic Institute |
|
| Type of Resource: | text | |
| Genre: | Article | |
| Date Issued: | 1991 | |
| Publisher: | Lippincott, Williams & Wilkins | |
| Place of Publication: | Baltimore, MD | |
| Physical Form: | ||
| Extent: | 7 p. | |
| Language(s): | English | |
| Identifier: | FA00007256 (IID) | |
| Note(s): |
The in vivo immunosuppressive properties of a novel, marine-derived compound, discodermolide, are reported here. Discodermolide was effective in suppressing the graft-versus-host splenomegaly response of BALB/c----CB6F1 (BALB/c X C57BL/6J)F1 grafted mice at 5.0, 2.5, and 1.25 mg/kg, when administered as daily, i.p. injections, for 7 days. Mice treated with 5.0 and 2.5 mg/kg demonstrated a high degree of suppression (219 and 150%, respectively); however, these dosages were associated with some degree of morbidity (2/5 and 4/5 survivors for 5.0 and 2.5 mg/kg, respectively). Mice that were treated with 1.25, 0.625, and 0.313 mg/kg remained healthy after a 7-day regimen, and continued to demonstrate suppression of splenomegaly (106%, 72%, and 76% suppression, respectively). Splenocytes obtained from discodermolide-treated, allogeneic grafted mice were suppressed in their ability to respond in vitro to optimal mitogenic concentrations of concanavalin A, and natural-killer-cell activity directed against YAC-1 tumor cells, compared with vehicle-treated, allogeneic grafted control mice. Lower dosages (2.5 and 1.25 mg/kg) of discodermolide, however, did not affect the subsequent ability of splenocytes obtained from these mice to produce IL-2 following in vitro stimulation with Con A. This was observed to be in contrast to the immunosuppressive activity observed with cyclosporine treatment of mice (150 mg/kg) for the ex vivo suppression of splenocyte production of IL-2. Treatment of normal, nongrafted mice with similar high dosages of discodermolide (5.0 mg/kg) for 4 days did not affect the primary antibody response of mice immunized with sheep red blood cells as measured by hemagglutination activity of their serum. These results suggest that discodermolide's in vivo immunosuppressive action appears not to be that of a generalized immunosuppressive agent and that its specific in vivo mechanism of action warrants further preclinical evaluation. Florida Atlantic University. Harbor Branch Oceanographic Institute contribution 829 This manuscript is an author version with the final publication available and may be cited as: Longley, R. E., Caddigan, D., Harmody, D., Gunasekera, M., & Gunasekera, S. P. (1991). Discodermolide-a new, marine-derived immunosuppressive compound. II. In vivo studies. Transplantation, 52(4), 656-661. |
|
| Subject(s): |
Polyketides Immunosuppressive agents Marine natural products discodermolide |
|
| Persistent Link to This Record: | http://purl.flvc.org/fau/fd/FA00007256 | |
| Host Institution: | FAU |
