TI-31, at concentrations of 10 and 100 microM, suppressed the antibody response to T cell-dependent (sheep red blood cells, SRBC) and -independent antigens (trinitrophenyl-lipopolysaccharide, TNP-LPS and TNP-Ficoll). The anti-SRBC response was suppressed by TI-31 when T cells were replaced by a supernatant of concanavalin A (Con A)-stimulated spleen cells, indicating the drug had influence on T lymphocytes, B lymphocytes and macrophages. TI-31 augmented the Con A-induced suppressor T cell (Ts) assessed by anti-SRBC plaque-forming cells response in vitro. The drug (10 mg/kg, p.o.) potentiated antigen specific Ts induction in vitro after injection of a high dose of SRBC. The results demonstrate that TI-31 enhanced Ts induction, which resulted in a diminution of antibody formation.

01 Apr 1987·Immunopharmacology

Inhibitory effect of TI-31 on autoimmune nephritis in NZB/NZW F1 mice through regulation of the immune response

Article

Author: Yamamoto, Itaru ; Hosoda, Kenji ; Kunisawa, Keiko ; Koyama, Tamotsu ; Takeshita, Toru ; Komoriya, Keiji ; Naruchi, Tatsuyuki ; Tsuchimoto, Masahiro ; Nagata, Ikuo

TI-31 (TEI-3096; 6-p-chlorobenzyl-5H-2,3,6,7-tetrahydro-5,7-dioxothiazolo[3,2-a]pyr imidine) is a novel immunomodulator. Various nephritic changes observed in female NZB/NZW F1 (B/W) mice with aging were suppressed by TI-31 when administered orally 5 times per week for 16 weeks at doses of 2, 10, or 50 mg/kg. It suppressed proteinuria, oliguria, the decrease of erythrocyte count, and increase of serum urea nitrogen, immune complex and anti-double-stranded DNA antibody levels. The anti-nephritic effect of TI-31 was confirmed by histopathological evaluation. TI-31 (10 mg/kg) could improve both the elevated polyclonal B cell activation and the depressed antibody response to sheep red blood cells in B/W mice, in comparison with age- and sex-matched BALB/c mice, without any effect on the antibody response in these normal mice. These findings indicate that TI-31 may inhibit B/W nephritis by regulating the antibody production through a mechanism different from that of anti-inflammatory drugs or immunosuppressants.

01 Jan 1987·The Japanese Journal of Pharmacology

Anti-arthritic and immunoregulatory effects of TI-31 on collagen-induced arthritis.

Article

Author: Keiji Komoriya ; Keiko Kunisawa ; Tatsuyuki Naruchi ; Ikuo Nagata ; Toru Takeshita

TI-31 (TEI-3096, 6-p-chlorobenzyl-5H-2,3,6,7-tetrahydro-5,7-dioxothiazolo[3,2-a]pyr imidine) reduced bovine type II collagen-induced arthritis (CIA) in rats in a time- and dose-dependent manner. Oral TI-31 treatment in doses of 10 and 50 mg/kg daily for 7 days prior to collagen immunization depressed the development of arthritis. However, it had no obvious effect on CIA when administered daily for a 7-day or 28-day period after the immunization. This compound was also ineffective against the established arthritis. On the contrary, cyclophosphamide, dexamethasone, or ibuprofen strongly protected the animals from the development of arthritis and/or cured the established arthritis by these dose regimens. Both humoral and delayed-type hypersensitivity skin responses to bovine type II collagen were decreased in rats treated with TI-31 daily for 7 days before the induction of arthritis. These results suggest that TI-31 depresses CIA by regulating the immune response to collagen through a mechanism different from that of anti-inflammatory drugs or immunosuppressants.

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Indication	Highest Phase	Country/Location	Organization	Date
Rheumatic Diseases	Phase 3	-	Beijing Tide Pharmaceutical Co., Ltd.	-
Rheumatic Diseases	Phase 3	-	Nxera Pharma Co., Ltd.	-

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