Measurement of Interleukin-6 Production by Monocytes for in Vitro Safety Testing of Hemoglobin Solutions

Induction of interleukin-6 (IL-6) production by isolated human mononuclear blood cells was taken as in vitro model for the induction of inflammatory reactions. The model was very sensitive to bacterial endotoxin (detection limit < 10pg/ml). Hemoglobin (Hb) solutions, prepared under non-sterile conditions also induced IL-6 production, which correlated with a positive reaction in the Limulus assay. Purification of the Hb solutions with a detergent prevented IL-6 production, showing that pure Hb itself does not activate the monocytes. We conclude that this assay is a useful and sensitive test of contamination with components that can induce inflammatory reactions, especially microbial products.