Virus-Induced Interferon Production by Human Macrophages

Abstract

Abstract The presence of interferon during viral infection in humans has been associated with the onset of the recovery process. The identity of the cell responsible for production of interferon in response to live virus has not been determined. Human peripheral blood mononuclear leukocytes, highly purified macrophages, and highly purified lymphocytes were exposed in vitro to influenza A virus. Interferon activity was detectable in the supernatant culture fluids of virus-exposed mononuclear leukocytes by 24 hr, was maximum by 72 to 96 hr, and declined thereafter. In each of eight experiments, supernatant fluid of virus-exposed macrophages contained interferon (100 to 800 units/ml, median 200 units/ml), but in none of the experiments was interferon detected in the supernatant fluid of control macrophages or virus-exposed or control lymphocytes. The interferon had characteristics of classical, Type I, interferon, and its activity was neutralized by rabbit antihuman leukocyte interferon globulin. Appearance of interferon activity in the supernatant fluid could not be attributed to cell death with release of preformed material. Adding lymphocytes to macrophages resulted in no increase in interferon activity in supernatant fluids in response to virus exposure, compared to macrophages alone. The results suggest a mechanism by which human macrophages may play an important role in human defense.