International collaborative study of the candidate international standards for human tumour necrosis factors alpha (hTNF-α) and beta (hTNF-β) and for murine tumour necrosis factor alpha (mTNF-α)

Abstract

Four ampouled preparations of human tumour necrosis factor alpha (hTNF-α), one ampoule of human tumour necrosis factor beta (hTNF-β) and one ampoule of mouse tumour necrosis factor alpha (mTNF-α) were evaluated by 20 laboratories in nine countries for their suitability to serve as international standards for these materials. A further three preparations of recombinant hTNF-α were included in the study so that hTNF-α preparations from different sources and with various structures could be compared. The preparations were assayed using in vitro bioassays and immunoassays. On the basis of the results reported here, with the agreement of participants in the study and with the authorisation of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO), the preparation of hTNF-α in ampoules designated 87/650 was established as the international standard for hTNF-α with a defined potency of 40 000 international units per ampoule. Estimates relative to hTNF-α for both hTNF-β and mTNF-α showed a substantial inter-laboratory variability in cytotoxic activity indicating that no preparations of hTNF-α would be suitable as a reference standard for either hTNF-β or mTNF-α. However, given the current need for reference preparations for these materials, the ampouled preparations of hTNF-β (87/640) and mTNF-α (88/532) were assigned potencies in arbitrary units and are available as reference reagents.