Toxicological and immunological evaluation of the immunosuppressant 15-deoxyspergualin in BALB/c mice: an in vivo and in vitro study.
The toxicological aspects as well as the immunosuppressive mechanism of 15-deoxyspergualin (DSP) were studied using BALB/c mice. Five-week-old animals were subcutaneously given phosphate-buffered saline (PBS; Group 1) or DSP at 0.5 (Group 2) to 5.0 mg (Group 4) per kg body weight daily for 1 to 3 months. They were sacrificed to obtain blood for hematology and liver function studies. The spleen, taken simultaneously, was histologically examined, the T cell surface markers of splenocytes were flow cytometrically measured, and their interleukin 2 (IL-2) production induced in vitro by Enterotoxin A (Ent A) was assayed using CTLL cells. Additionally, the in vitro effect of DSP on IL-2 generation and plaque forming cell (PFC) production was studied using splenocytes of non-treated mice. During the 3 months of treatment, the body weight slowly increased in Groups 1 and 2, while the body weight of the 2.5-mg DSP mouse group (Group 3) was significantly lower on days 28 and 56 of treatment compared with Group 1 of the same age (P less than 0.05). The administration of DSP at 5.0 mg/kg (Group 4) caused marked reduction in body weight of the animals. They were sacrificed on day 28 because of their worsening general condition. WBC and RBC counts decreased in Group 3 on days 57 and 93, and the platelet number increased on day 57. A liver function test was not affected by DSP treatment except for an elevated SGOT in Group 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Okubo
M
M
Department of Medicine, Kitasato University School of Medicine, Japan.
Amemiya
K
K
Kamata
K
K
Sato
N
N
Horata
E
E
Masaki
Y
Y
Uchiyama
T
T
Aoyagi
T
T
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects; D001773:Blood Cells / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000633:toxicity; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects
D006146:Guanidines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; C037258:gusperimus