HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Induction of suppressor cell activity in vivo and suppression of lymphoproliferative responses in vitro by SK&F 105.685 in the dog.

Abstract
SK&F 105.685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine+ ++ dihydrochloride) is a novel azaspirane with beneficial activity in rat models of adjuvant-induced arthritis and experimental autoimmune encephalomyelitis as well as in the murine lupus model. The mechanism of action in these models appears to be the induction of non-specific suppressor cell activity which is measured by the ability of cells from treated animals to partially inhibit the proliferative response of lymphocytes from control animals to concanavalin A (ConA) in a co-culture assay. In this study we have shown that oral administration of 0.1-3 mg/kg/day of SK&F 105.685 to purebred beagle dogs induced suppressor cell activity in the spleen and bone marrow but not in the peripheral blood. In vitro, SK&F 105.685 partially suppressed the proliferative response of dog splenocytes to the mitogens phytohemagglutinin (PHA), ConA and, to a lesser extent, pokeweed mitogen (PWM). Peripheral blood lymphocytes (PBLs) differed from spleen cells in their susceptibility to suppression by SK&F 105.685. While the PWM and ConA responses of PBLs and spleen cells showed similar levels of inhibition, the PHA response of PBLs, in marked contrast to spleen cells, was resistant to suppression by the compound. Our results show that the immunoregulatory effects of SK&F 105,685 are not limited to rodents and that suppressor cell activity in dogs is induced quickly and by relatively low doses of the compound.
AuthorsP A Thiem, J M Kaplan, P J Bugelski, E V Ruggieri, A M Badger
JournalImmunopharmacology (Immunopharmacology) 1992 Mar-Apr Vol. 23 Issue 2 Pg. 67-74 ISSN: 0162-3109 [Print] Netherlands
PMID1534791 (Publication Type: Journal Article)
Chemical References
  • Adjuvants, Immunologic
  • Spiro Compounds
  • SK&F 105685
Topics
  • Adjuvants, Immunologic (pharmacology)
  • Animals
  • Bone Marrow (drug effects, immunology)
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • In Vitro Techniques
  • Lymphocyte Activation (drug effects)
  • Male
  • Spiro Compounds (administration & dosage, pharmacology)
  • Spleen (drug effects, immunology)
  • T-Lymphocytes, Regulatory (drug effects, immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: