Prolongation of murine thyroid allografts by interleukin 2 (DAB486)-toxin and RS-61443.
We evaluated the efficacy of interleukin 2 (DAB486)-toxin (IL-2-diphtheria toxin fusion protein; IL-2-toxin) in combination with RS-61443 to prolong murine thyroid allograft survival. B10.BR thyroid allografts were transplanted beneath the renal subcapsule in recipient (C57BL/10 mice and graft survival determined 21 days later. Treatment with IL-2-toxin (25 microg/day for 14 days) was unable to prolong graft survival significantly. RS-61443 treatment (21 days) achieved significant graft prolongation only at doses of 300 mg/kg daily or greater. When both drugs were used in combination (IL-2-toxin, 25 microg/day for 14 days RS-61443 200 mg/kg daily for 21 days), statistically significant (P < 0.0001) graft prolongation was obtained. Our results suggest that IL-2-toxin in combination with subtherapeutic RS-61443 levels significantly prolongs murine thyroid allograft survival. IL-2-toxin and RS-61443, because of their unique and complementary mechanisms, hold promise for more selective immunosuppression.
Hullett
D A
DA
Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA.
Landry
A S
AS
Eckoff
D E
DE
Nichols
J C
JC
Eugui
E M
EM
Allison
A C
AC
Sollinger
H W
HW
D000818:Animals; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000922:Immunotoxins / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
C054780:DAB(486)-interleukin 2; D004167:Diphtheria Toxin; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D009173:Mycophenolic Acid