Targeted suppression of cytokine production in monocytes but not in T lymphocytes by a tetravalent guanylhydrazone (CNI-1493)

J Infect Dis. 1997 Nov;176(5):1303-12. doi: 10.1086/514126.

Abstract

Image analysis was used to study the cytokine-inhibitory effect of the nitric oxide inhibitor tetravalent guanylhydrazone (CNI-1493) in individual immunocytochemically stained human peripheral blood mononuclear cells (PBMC). CNI-1493 inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-8 production whether or not LPS stimulation was enhanced by interferon (IFN)-gamma priming. Addition of TNF-alpha to CNI-1493-exposed LPS-stimulated cells partially restored the incidence of IL-1alpha-, IL-1beta-, and IL-8-producing cells. TNF-alpha production induced by costimulation by ligation of CD3 and CD28 was inhibited by CNI-1493 in monocytes but not in T lymphocytes. The prevalence of IL-2-, IFN-gamma-, and TNF-beta-producing T cells was not reduced by CNI-1493. Phorbol ester and ionomycin activation also resulted in a CNI-1493 -induced inhibition of TNF-alpha in monocytes but resistant production of TNF-alpha, IL-2, and IFN-gamma by T cells. Thus, CNI-1493 preferentially inhibited synthesis of proinflammatory cytokines in monocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Humans
  • Hydrazones / pharmacology*
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-1 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Lymphocyte Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Cytokines
  • Hydrazones
  • Immunosuppressive Agents
  • Interleukin-1
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • semapimod