Effect of tacrolimus derivatives on immunosuppression.
In this study, the effects of the FK506-mPEG on immune cell activity, skin grafting rejection, and Freund's complete adjuvant arthritis were investigated. The proliferation of T cells was inhibited with increase with the FK506 and FK506-mPEG concentrations. FK506 and FK506-mPEG at concentrations between 0.01 nM and 1000 nM had very similar effects on the proliferation of the T cells. On the other hand, in the case of the proliferation of T cells by calcium ionophore A23187 (1 microM), when the FK506-mPEG concentration was increased from 0.01 to 1000 mM, the proliferation was decreased from 90.8 to 40.3%. This was 1.8-fold higher than that of paramethoxyamphetamine (PMA). The inhibitory effect of FK506-mPEG on mast cell proliferation was higher than that of FK506. When B cells were cultured for 7 days in basal medium with no pokeweed mitogen (PWM), the IgG production was 156.2 ng/mL. On the other hand, in the case of the same treatment with 0.25% of PWM, it was 876.4 ng/mL. This is about 5.6-fold higher than with no PWM. These results show that FK506-mPEG may be practically applicable as a prodrug for the immunosuppressant FK506.
Choi
Dubok
D
Department of Environmental Health, Cho-dang University, Chonnam, 534-800, Korea. hcho@chosun.ac.kr
Cho
Hoon
H
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005620:Freund's Adjuvant; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D016038:Skin Transplantation / Q000009:adverse effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors
D007166:Immunosuppressive Agents; D011355:Prodrugs; D011092:Polyethylene Glycols; D005620:Freund's Adjuvant; D016559:Tacrolimus