The potentiating effect of LPS on tumor necrosis factor-alpha production by influenza A virus-infected macrophages

• Published in: Immunobiology (1979) Vol. 187; no. 3-5; p. 357
• Main Authors: Bender, A, Sprenger, H, Gong, J H, Henke, A, Bolte, G, Spengler, H P, Nain, M, Gemsa, D
• Format: Journal Article
• Language: English
• Published: Netherlands 01.04.1993
• Subjects: Animals; Cell Death; Cell Line; Dinoprostone - biosynthesis; Electrophoresis, Polyacrylamide Gel; Gene Expression; Humans; Immunoblotting; Influenza A virus - physiology; Interferons - biosynthesis; Lipid A - immunology; Lipopolysaccharides - immunology; Macrophages - immunology; Monocytes - immunology; RNA, Messenger - analysis; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Virus Replication
• ISSN: 0171-2985
• DOI: 10.1016/S0171-2985(11)80350-5

Infection of murine PU5-1.8 macrophages and human monocytes by influenza A virus was associated with virus replication, release of tumor necrosis factor-alpha (TNF-alpha) and subsequent cell death. In the presence of small and by itself rather inefficient concentrations of lipopolysaccharide (LPS) or free lipid A (1 to 10 ng/ml), TNF-alpha production of virus-infected macrophages was strongly potentiated. LPS-triggered and enhanced TNF-alpha release from virus-infected macrophages was neither due to increased cell survival nor altered virus replication, potentiated TNF-alpha gene transcription, release of intracellularly stored TNF-alpha or shifts in the kinetics of TNF-alpha secretion. Influenza A virus infection alone induced a massive TNF-alpha mRNA accumulation which, however, was only weakly translated into bioactive TNF-alpha protein. When these virus-primed macrophages were exposed to LPS either simultaneously or up to 4 h after infection, an efficient and high translation into TNF-alpha protein occurred. Although the LPS-induced biochemical pathways leading to an augmented TNF-alpha production by virus-infected macrophages still remains unsolved, the findings suggest that the frequently observed serious clinical complications in the course of combined influenza A virus and bacterial infections may be due, at least in part, to an excessive release of cytokines such as TNF-alpha.