The detection of pyrogens in blood products using an ex vivo whole blood culture assay.

Induction of interleukin-6 (IL-6) secretion by whole blood cultures (WBC) was used as an in vitro assay system for pyrogen-induced inflammatory reactions. The assay system was very sensitive to Eschericia coli (E coli) endotoxin (< 10 pg/ml). The potential pyrogenic effects of human serum albumin (HSA), Fibronectin (Fn) and stabilised human serum (SHS) solutions were analyzed using this system. None of the products assayed had an effect on the sensitivity of the WBC assay. Spike recovery studies with isolated endotoxin, gram positive and gram negative bacteria showed that none of the products had an effect on the spike recovery of these pyrogenic substances. Good correlations were found between the WBC assay and the rabbit assay for pyrogens for all the production batches tested. When these samples were analysed by the limulus amoebocyte lysate (LAL) assay, the LAL test gave anomalous results for 1 out of the 22 production batches tested. This batch gave a false negative result on the LAL assay and might be indicative of the inability of the LAL assay to detect pyrogens other than endotoxin.