Effect of respiratory syncytial virus-antibody complexes on cytokine (IL-8, IL-6, TNF-alpha) release and respiratory burst in human granulocytes.

The release of interleukin-8 (IL-8), IL-6, and tumour necrosis factor-alpha (TNF-alpha) from human polymorphonuclear granulocytes (PMN) after exposure to infectious respiratory syncytial virus (RSV) particles was investigated. Our data showed that PMN secreted IL-8 and IL-6 in a time- and RSV-dose-dependent manner. During the RSV exposure, TNF-alpha was not detected in the cell supernatant of PMN. Similar amounts of IL-8 were secreted after either incubation with infectious or UV-inactivated RSV particles. Obviously, PMN bind and phagocytose the viral particles, which leads to the secretion of cytokines. The increased IL-8 secretion was accompanied with an enhanced cytoplasmic IL-8 mRNA steady state level, as shown by Northern blot analysis. The IL-8 secretion pattern from PMN was also studied after its interaction with RSV--antibody complexes. Non-neutralizing monoclonal antibodies (mAb) directed to the RSV fusion protein and glycoprotein were used to generate immune complexes. Only the mAb directed to the RSV fusion protein enhanced the IL-8 release from PMN significantly. In addition, the chemiluminescence response from PMN was analysed after exposure of the cells to RSV particles, RSV-mAb complexes, Ca-ionophore A23187 or N-formyl-methionyl-leucyl-phenylalanine (FMLP). The phagocytosis of RSV inhibited the oxygen radical production induced by the Ca-ionophore A23187 or FMLP. Only RSV-anti-fusion protein mAb complexes generated a chemiluminescence response from PMN. Thus, PMN play an important role in the control of RSV infection.