TNF-alpha release from human peripheral blood mononuclear cells to predict the proinflammatory activity of cytokines and growth factors.
Therapeutic applications of novel growth factors and cytokines can be limited due to the oftentimes severe inflammatory reactions that are encountered in patients following parenteral administration. These inflammatory responses, hallmarked by fever, headache, and chills are mediated by the release of inflammatory cytokines following administration of protein-based therapeutics. TNF-alpha appears to be one of the most potent and pleiotropic inflammatory cytokines released during the early stages of an inflammatory response. In the present study, we have explored the use of an in vitro assay system to determine whether the release of TNF-alpha from human PBMC could be correlated with documented inflammatory activity in humans. The cytokines tested included rhGM-CSF, rhIL-2, rhIL-3, and rhIFN-gamma, rhG-CSF, which has been shown to lack substantial proinflammatory activity in humans, was also tested. The potent macrophage activator and inflammatory agent, LPS, was used as a positive control. Results of this study demonstrate and confirm an association between the inflammatory activity of cytokines observed in patients and the stimulation of TNF-alpha release from PBMC in vitro. This assay system can be used as a predictive tool in determining the inflammatory potential of novel growth factors and cytokines.
Oshiro
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Product Safety Assessment, R and D, Searle, Skokie, IL 60077, USA.
Morris
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DL
D016207:Cytokines / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000276:immunology; D006133:Growth Substances / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000009:adverse effects / Q000276:immunology; D007376:Interleukin-2 / Q000009:adverse effects / Q000276:immunology; D007377:Interleukin-3 / Q000009:adverse effects / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor