Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection

Many of the major alterations in plasma proteins characteristic of the hepatic acute phase response are regulated by IFN-beta 2/IL-6. Using a specific bioassay for IFN-beta 2/IL-6, which relies on the induction of the hepatic acute phase plasma protein alpha 1-antichymotrypsin in the human hepatoma cell line Hep3B clone 2 and its inhibition by anti-rIFN-beta 2/IL-6 antiserum, we have detected high levels of IFN-beta 2/IL-6 in the body fluids of patients with acute bacterial infections. Cerebrospinal fluid from four patients with acute bacterial meningitis (Streptococcus pneumoniae, Staphylococcus aureus, two cases of Listeria monocytogenes) all had high levels of IFN-beta 2/IL-6 (up to 500 ng/ml). Two of these patients with concomitant bacteremia had lower concentrations of IFN-beta 2/IL-6 in the serum (5 to 70 ng/ml). Three additional patients with Escherichia coli, Pseudomonas aeruginosa, and Neisseria meningitidis bacteremia had high levels of serum IFN-beta 2/IL-6, as did the ankle fluid of a patient with Streptococcus canis arthritis. Normal cerebrospinal fluid and serum had little detectable IFN-beta 2/IL-6. A combination of immunoaffinity chromatography and immunoblotting procedures were used to characterize the IFN-beta 2/IL-6 species present in a representative sampling of serum and cerebrospinal fluids. Multiple immunoreactive species of IFN-beta 2/IL-6 in the size range 23 to 30 kDa as well as immunoreactive complexes in the range 60 to 70 kDa were detected in human body fluids. This is the first demonstration that previous descriptions of heterogeneity in human IFN-beta 2/IL-6 species produced in cell culture correspond to observations in the infected host.