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) afte r exposure to infectious respiratory syncytial virus (RSV) particles w as investigated. Our data show that PMN secreted IL-8 and IL-6 in a ti me- 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-inactiv ated RSV particles. Obviously, PMN bind and phagocytose the viral part icles, which leads to the secretion of cytokines. The increased IL-8 s ecretion was accompanied with an enhanced cytoplasmic IL-8 mRNA steady state level, as shown by Northern blot analysis. The IL-8 secretion p attern from PMN was also studied after its interaction with RSV-antibo dy complexes. Nonneutralizing monoclonal antibodies (mAb) directed to the RSV fusion protein and glycoprotein were used to generate immune c omplexes. Only the mAb directed to the RSV fusion protein enhanced the IL-8 release from PMN significantly. In addition, the chemiluminescen ce response from PMN was analysed after exposure of the cells to RSV p articles, RSV-mAb complexes, Ca-ionophore A23187 or N-formyl-methionyl -leucyl-phenylalanine (FMLP). The phagocytosis of RSV inhibited the ox ygen radical production induced by the Ca-ionophore A23187 or FMLP. On ly RSV-anti-fusion protein mAb complexes generated a chemiluminescence response from PMN. Thus, PMN play an important role in the control of RSV infection.