Immunopharmacological studies of PTT.119, a new synthetic bis-(2-chloroethyl)amino-L-phenylalanine derivative.
The new synthetic tripeptide p-F-Phe-m-bis-(2-chloro-ethyl)amino-Phe-Met-etoxy HCl, PTT.119, was studied for its effects on the host immune system. Doses of PTT.119 ranging from 3 to 18 mg/kg were administered i.p. to recipient mice which, at different times after drug treatment, were tested for allograft response, competence in producing lymphocytes active in lethal graft-versus-host disease, delayed-type hypersensitivity, mitogen responsiveness, humoral antibody production and natural resistance against microbial infections. At therapeutically active dosages, PTT.119 appeared to selectively inhibit functions mediated by B lymphocytes, leaving the majority of those involving T-cell subsets largely unaffected, even at the highest doses employed. Moreover, drug treatment had also a limited impact on the in vivo resistance of mice to microbial infection, which was only affected by a drug injection of 18 mg/kg, a dose well within the confidence limits of the mean lethal dose of the drug.
Allegrucci
M
M
Inst. of Pharmacology, Univ. of Perugia, Italy.
Ballerini
P
P
Romani
L
L
Frati
L
L
D000818:Animals; D000917:Antibody Formation; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000628:therapy; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007109:Immunity / Q000187:drug effects*; D007111:Immunity, Cellular; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000276:immunology*
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C038259:ambamustine