Effect of a novel immunosuppressant, ST1959, on the immune system and renal allograft survival in rats.
BACKGROUND
ST1959 is a 3,5-diaryl-s-triazole belonging to a novel class of contragestional agents with immunosuppressant activity. The aim of the present study was to investigate the effects of this drug on allogeneic immune response and on renal allograft survival in rats.


METHODS
One group of naive and one group of allosensitized Lewis rats received ST1959 (0.5 mg/kg/day for 6 days administered subcutaneously). The respective control groups received vehicle alone. At the end of treatment, all rats were killed and thymus, spleen, lymph nodes, bone marrow, and blood were harvested. Cell number, leukocyte subpopulations, and lymphocyte alloreactivity were evaluated. Three additional groups of Lewis rats received an allogeneic (Brown Norway [BN]) kidney transplant: two groups received ST1959 (0.5 mg/kg daily until death or for 6 days and then twice weekly), and the last one received vehicle.


RESULTS
In naive rats, ST1959 reduced the percentage of CD4CD8 (74.2+/-2.7%; vehicle, 89.1+/-1.1%; P<0.05) and increased the percentage of CD4CD8 thymocytes (5.7+/-0.8% vs. 2.8+/-0.4%; P<0.05). Infusion of allogeneic (BN) splenocytes caused a twofold increase of activated CD4 T cells (CD4CD25) that was prevented by ST1959 treatment. Consistently, the alloreactivity of lymphocytes from naive and allosensitized animals treated with ST1959 was significantly lower than that of control rats. ST1959 (in both tested regimens) significantly prolonged renal allograft survival in comparison with vehicle (12.4+/-0.5 vs. 7.7+/-0.5 days; P<0.001).


CONCLUSIONS
ST1959 possesses immunomodulatory effects and significantly prolongs survival of renal allografts in rats.
Pezzotta
Anna
A
Transplant Research Center Chiara Cucchi de Alessandri e Gilberto Crespi, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Bergamo, Italy.
Mister
Marilena
M
Cravedi
Paolo
P
Azzollini
Nadia
N
Cassis
Linda
L
Ruggiero
Vito
V
DeSantis
Rita
R
Carminati
Paolo
P
Remuzzi
Giuseppe
G
Noris
Marina
M
D000818:Animals; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008198:Lymph Nodes / Q000033:anatomy & histology / Q000276:immunology; D008297:Male; D009929:Organ Size; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000033:anatomy & histology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*; D014230:Triazoles / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D014230:Triazoles; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole