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Lars Björk, Kevin J. Tracey, Peter Ulrich, Marina Bianchi, Pamela S. Cohen, Karin Åkerlund, Thomas E. Fehniger, Ulf Andersson, Jan Andersson, Targeted Suppression of Cytokine Production in Monocytes but Not in T Lymphocytes by a Tetravalent Guanylhydrazone (CNI-1493), The Journal of Infectious Diseases, Volume 176, Issue 5, November 1997, Pages 1303–1312, https://doi.org/10.1086/514126
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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.