The present study investigates the potential capacity of the immunostimulant Corynebacterium parvum (C.p.) to induce tumor necrosis factor-alpha (TNF-alpha) in human peripheral blood mononuclear cells (PBMC) and blood monocytes (BMo) in vitro. Both at the mRNA and protein level, stimulation of PBMC and BMo upon C.p. induces TNF-alpha. Compared to the hitherto used TNF-alpha inducers in vitro such as Sendai virus, phytohemagglutinin or lipopolysaccharide the C.p. stimulus displayed a threefold stronger induction of TNF-alpha production (p less than 0.001). Using C.p. as an inducer it was possible to demonstrate that TNF-alpha production is regulated by prostaglandin E2; preincubation of the cells with prostaglandin E2 resulted in a reduced C.p.-mediated TNF-alpha production (p less than 0.001). Coincubation of interferon-gamma (IFN-gamma) together with C.p. led to an enhanced release of TNF-alpha, supporting the assumption that C.p. is a potent TNF-alpha inducer. The additive effect of IFN-gamma and TNF-alpha on the receptor level was demonstrated by addition of IFN-gamma antibodies to the PBMC cultures. Under these conditions TNF-alpha production, stimulated by C.p. and IFN-gamma, was decreased by 30%, compared to the production in assays supplemented with C.p. alone. From these data we conclude that C.p. is a new inducer of TNF-alpha in vitro and a useful tool to study TNF-alpha production of PBMC and BMo from either healthy donors or from patients.

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http://dx.doi.org/10.1002/eji.1830200821DOI Listing

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