Matches in SemOpenAlex for { <https://semopenalex.org/work/W2605097000> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W2605097000 abstract "Development of immune-modulating drugs is challenging as assessment of intended pharmacology in healthy volunteers is difficult. Commonly, ex-vivo LPS challenges of whole blood or isolated cells are applied. However, the applicability of the LPS challenge is limited as LPS primarily stimulates germ-line encoded innate-immune TLR4-receptors, and thus does not allow monitoring of pharmacological modulation of the adaptive immune compartment. We explored an alternative whole blood challenge, inducing lymphocyte-driven inflammation by the superantigen staphylococcal enterotoxin B (SEB), and compared this to LPS. Further validation was performed by assessing the inhibitory effects of different immune-modulating compounds (MAP kinase inhibitors, calcitriol, methotrexate, protein kinase C, doxycycline, simvastatin), allowing discrimination between effects on monocytes and lymphocytes. SEB induction resulted in the release of a cytokine panel that well-resembled cytokine release observed after physiological lymphocyte stimulation, with clear induction of IL-2, IFN-γ, TNF- α, IL-10 and GM-CSF. Based on TNF-α and IL-2 release, SEB’s maximal effect was reached at 100 ng/mL. Whereas inter-individual variability in EC50 was relatively small for LPS (0.32±0.10 ng/mL), for SEB inter-subject variability was distinctly higher (62±54 ng/mL). MAP kinase inhibitors and calcitriol were effective in inhibiting SEB-induced TNF-α and IL-2 release, demonstrating an inhibitory effect on the monocyte and/or lymphocyte. Importantly, whereas methotrexate, doxycycline, and simvastatin did not affect SEB-induced TNF-α release, a clear inhibiting effect on SEB-induced IL-2 release was observed, implying a direct action of these compounds on the lymphocyte. These data demonstrate that the SEB challenge can be used to estimate the immune-modulating effects of compounds directly acting on the T-lymphocyte population. As such, the whole blood SEB challenge is a useful translational tool in early drug development, especially since immune-inflammation is a target in the development of new treatment modalities for currently poorly-controlled diseases such as rheumatoid arthritis and psoriasis, and cardiovascular disease." @default.
- W2605097000 created "2017-04-14" @default.
- W2605097000 creator A5021841624 @default.
- W2605097000 creator A5025768536 @default.
- W2605097000 creator A5037914796 @default.
- W2605097000 creator A5054138172 @default.
- W2605097000 creator A5083164288 @default.
- W2605097000 date "2013-05-01" @default.
- W2605097000 modified "2023-09-26" @default.
- W2605097000 title "Abstract 316: A Superantigen Whole Blood Challenge Test for the Quantification of Immuno-inflammation in Early Phase Drug Development" @default.
- W2605097000 doi "https://doi.org/10.1161/atvb.33.suppl_1.a316" @default.
- W2605097000 hasPublicationYear "2013" @default.
- W2605097000 type Work @default.
- W2605097000 sameAs 2605097000 @default.
- W2605097000 citedByCount "0" @default.
- W2605097000 crossrefType "journal-article" @default.
- W2605097000 hasAuthorship W2605097000A5021841624 @default.
- W2605097000 hasAuthorship W2605097000A5025768536 @default.
- W2605097000 hasAuthorship W2605097000A5037914796 @default.
- W2605097000 hasAuthorship W2605097000A5054138172 @default.
- W2605097000 hasAuthorship W2605097000A5083164288 @default.
- W2605097000 hasConcept C150903083 @default.
- W2605097000 hasConcept C17991360 @default.
- W2605097000 hasConcept C203014093 @default.
- W2605097000 hasConcept C207001950 @default.
- W2605097000 hasConcept C26291073 @default.
- W2605097000 hasConcept C2776070231 @default.
- W2605097000 hasConcept C2776090121 @default.
- W2605097000 hasConcept C2776914184 @default.
- W2605097000 hasConcept C2778690821 @default.
- W2605097000 hasConcept C2778754761 @default.
- W2605097000 hasConcept C36333154 @default.
- W2605097000 hasConcept C71924100 @default.
- W2605097000 hasConcept C86803240 @default.
- W2605097000 hasConcept C8891405 @default.
- W2605097000 hasConcept C98274493 @default.
- W2605097000 hasConceptScore W2605097000C150903083 @default.
- W2605097000 hasConceptScore W2605097000C17991360 @default.
- W2605097000 hasConceptScore W2605097000C203014093 @default.
- W2605097000 hasConceptScore W2605097000C207001950 @default.
- W2605097000 hasConceptScore W2605097000C26291073 @default.
- W2605097000 hasConceptScore W2605097000C2776070231 @default.
- W2605097000 hasConceptScore W2605097000C2776090121 @default.
- W2605097000 hasConceptScore W2605097000C2776914184 @default.
- W2605097000 hasConceptScore W2605097000C2778690821 @default.
- W2605097000 hasConceptScore W2605097000C2778754761 @default.
- W2605097000 hasConceptScore W2605097000C36333154 @default.
- W2605097000 hasConceptScore W2605097000C71924100 @default.
- W2605097000 hasConceptScore W2605097000C86803240 @default.
- W2605097000 hasConceptScore W2605097000C8891405 @default.
- W2605097000 hasConceptScore W2605097000C98274493 @default.
- W2605097000 hasIssue "suppl_1" @default.
- W2605097000 hasLocation W26050970001 @default.
- W2605097000 hasOpenAccess W2605097000 @default.
- W2605097000 hasPrimaryLocation W26050970001 @default.
- W2605097000 hasRelatedWork W1563900735 @default.
- W2605097000 hasRelatedWork W1978398769 @default.
- W2605097000 hasRelatedWork W2045074773 @default.
- W2605097000 hasRelatedWork W2046142379 @default.
- W2605097000 hasRelatedWork W2063834619 @default.
- W2605097000 hasRelatedWork W2073863642 @default.
- W2605097000 hasRelatedWork W2077917150 @default.
- W2605097000 hasRelatedWork W2774961326 @default.
- W2605097000 hasRelatedWork W4311969349 @default.
- W2605097000 hasRelatedWork W56206085 @default.
- W2605097000 hasVolume "33" @default.
- W2605097000 isParatext "false" @default.
- W2605097000 isRetracted "false" @default.
- W2605097000 magId "2605097000" @default.
- W2605097000 workType "article" @default.