In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 1_Supplement ( 2009-04-01), p. 47.18-47.18
Abstract:
The new European Union REACH (Registration, Evaluation and Authorisation of new and existing CHemicals) policy will increase the use of laboratory animals if alternative methods are not available. The immune system is a target for many chemicals and drugs, with potential adverse effects on human health. We performed an inter-laboratory pre-validation of a set of in vitro assays to detect immunosuppressive capacity. Human PBMC and murine and rat splenocytes were used. Six immunosuppressive compounds (benzo(a)pyrene, cyclophosphamide, methotrexate, rapamycin, dexamethasone, and urethane) and one non-immunosuppressive compound (D-mannitol) were tested. Basal cytotoxicity was assessed by measuring LDH-release. Human PBMC were stimulated with anti-CD3/anti-CD28, murine splenocytes with anti-CD3/anti-CD28, Con A, LPS, and anti-CD40/IL-4, and rat splenocytes with Con A and LPS. Cell proliferation and IFN-γ and TNF-α production were measured. Five out of 6 immunosuppressive compounds could be identified as such, and the non-immunotoxic one came out as negative. This suggests that in vitro assays are able to detect immunosuppressive capacity. The sensitivity of the various species/stimulant/endpoint combinations ranged between 38 and 61%, while the specificity ranged between 67 and 100%. This suggests that from these results a choice for specific species/stimulant/endpoint combinations cannot be made.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.182.Supp.47.18
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
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