Induction of non-specific suppressor cells and myeloregulatory effects of an immunomodulatory azaspirane, SK&F 105685

Andrew G. King, Diane Olivera, James E. Talmadge, Alison M. Badger

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Administration of the immunosuppressive agent, SK&F 105685, has demonstrated immunosuppressive activity in several animal models of autoimmunity such as adjuvant arthritis and experimental autoimmune encephalomyelitis. The mechanism of action of SK&F 105685 in these autoimmune disease models appears to be the induction of non-specific suppressor cells (SC) detected in the spleen and bone marrow of treated animals. In this study we have examined the kinetics of SC appearance in the spleen and bone marrow following treatment with 30 mg/kg/day, p.o., for 1-6 days. SC activity was apparent following a single dose and increased with successive treatments. Treatment with SK&F 105685 also resulted in significantly enhanced myelopoiesis as measured by a 128% increase in the frequency of bone marrow myeloid progenitors (CFU-GM). Mechanistic studies indicated that in vitro treatment of bone marrow stromal cell cultures with SK&F 105685 upregulated the production of colony stimulating activity (CSA) detectable in a rat CFU-GM assay. Further, in vitro studies revealed that the SC in the bone marrow or spleens of SK&F 105685-treated rats admixed with normal marrow cells inhibited CFU-GM formation at a six-fold less cell concentration than cells obtained from control rats. These in vitro results suggest that the SK&F 105685-induced myelopoiesis is regulated by the subsequent generation of SC.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalInternational Journal of Immunopharmacology
Volume13
Issue number1
DOIs
StatePublished - 1991

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Granulocyte-Macrophage Progenitor Cells
Bone Marrow
Myelopoiesis
Spleen
Immunosuppressive Agents
Experimental Arthritis
Autoimmune Experimental Encephalomyelitis
azaspirane
Autoimmunity
Mesenchymal Stromal Cells
Bone Marrow Cells
Autoimmune Diseases
Animal Models
Cell Culture Techniques
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Induction of non-specific suppressor cells and myeloregulatory effects of an immunomodulatory azaspirane, SK&F 105685. / King, Andrew G.; Olivera, Diane; Talmadge, James E.; Badger, Alison M.

In: International Journal of Immunopharmacology, Vol. 13, No. 1, 1991, p. 91-100.

Research output: Contribution to journalArticle

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