title: A model of human whole blood lymphokine release for in vitro and ex vivo use.
abstract: Endotoxin (lipopolysaccharide, LPS) inducible cytokine release by human whole blood is increasingly used to model inflammatory responses in vitro, to detect the presence of pyrogenic contaminations as well as to monitor disease states or immunomodulatory treatments ex vivo. However, the LPS-stimulated blood model primarily allows the assessment of monocyte responses. Here, a whole blood model was established which allows assessment of lymphocyte responses. Four different superantigens, namely staphylococcal enterotoxin A and B (SEA, SEB), toxic shock syndrome toxin-1 (TSST-1) or streptococcal exotoxin A (SPEA) were tested with respect to the induction of lymphokine release. All superantigens were capable of inducing significant amounts of the lymphokines interferon-gamma (IFNgamma), interleukin 2 (IL-2), IL-4, IL-5, IL-13 and tumor necrosis factor beta (TNFbeta) after 72 h of incubation. Concentration-dependencies and kinetics were determined. Blood from 160 healthy donors was used to assess the variability of SEB-inducible lymphokine release. Interindividual differences were more pronounced compared to LPS-inducible monokine release. However, the individual response was maintained when blood from six donors was tested once a week for 8 weeks, suggesting that the individual response represents a donor characteristic. The model appears to be suitable for the evaluation of immunomodulatory agents in vitro as well as ex vivo.
authors.affiliation: Biochemical Pharmacology, University of Konstanz, 78457, Constance, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Hermann
authors.forename: Sonja
authors.initials: S
authors.lastname: von Aulock
authors.forename: Kathrin
authors.initials: K
authors.lastname: Graf
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
mesh_terms: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005098:Exotoxins / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D007378:Interleukins / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000097:blood* / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000097:blood / Q000378:metabolism; D008565:Membrane Proteins; D018448:Models, Immunological; D018089:Superantigens / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D007378:Interleukins; D008070:Lipopolysaccharides; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; C027951:erythrogenic toxin; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma