Targeted Suppression of Cytokine Production in Monocytes but Not in T Lymphocytes by a Tetravalent Guanylhydrazone (CNI‐1493)

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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)-α, interleukin (IL)-1α, IL-1β, IL-6, and IL-8 production whether or not LPS stimulation was enhanced by interferon (IFN)-γ priming. Addition of TNF-α to CNI-1493-exposed LPS-stimulated cells partially restored the incidence of IL-1α-, IL-1β-, and IL-8-producing cells. TNF-α 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-γ-, and TNF-β-producingTcells was not reduced by CNI-1493. Phorbol ester and ionomycin activation also resulted in a CNI-1493-induced inhibition of TNF-ain monocytes but resistant production of TNF-α, IL-2, and IFN-γ by T cells. Thus, CNI-1493 preferentially inhibited synthesis of proinflammatory cytokines in monocytes.

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