Pyrogenic and haematological effects of the interferon-inducing 22K factor (interleukin 1 beta) from human leukocytes

Human 22K factor is a cytokine released by mitogen-stimulated peripheral blood leukocytes. The factor stimulates fibroblasts to produce interferon-beta (IFN-beta) and thereby exerts antiviral activity on these cells. It was identified as interleukin-1 beta (IL-1 beta) by its amino-acid sequence and spectrum of biological activities. The pyrogenic and haematological effects of pure 22K factor were studied at different doses and were compared with those of endotoxin and interferon. 22K factor dose-dependently induced fever in rabbits, 0.1 microgram/kg being a minimum effective dose. Intravenous injection in rabbits caused immediate granulocytosis at low dose, while a profound granulopenia followed by hypergranulocytosis was observed at high dose. Preparations of pure 22K factor were free of detectable lipopolysaccharide and lost their biological effects after heat-treatment. Repeated injections of 22K factor did not result in a state of tolerance. There is no evidence that the effects in vivo of 22K factor were mediated by induction of interferon. Human 22K factor, a weak and species-specific inducer in IFN-beta in vitro, did not induce detectable amounts of circulating interferon in rabbits. Moreover, injection of rabbits with IFN-beta resulted in a weak effect on body temperature and granulocyte counts as compared to similar doses of 22K factor.