Human influenza virus neuraminidase, but not hemagglutinin, induces murine macrophage interleukin 1 in vivo and in vitro.

Since our previous studies showed that the viral glycoproteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA), are involved in stimulating the human and mouse natural killer (NK) cell activities, it was considered appropriate to study the effect of these glycoproteins on macrophages, another component of nonspecific resistance mechanisms. The glycoproteins HA and NA, of the strain A/USSR/90/77 (H1N1), were purified electrophoretically and were tested in vitro using the adherent peritoneal macrophages of C3H/HeN mice elicited with thioglycolate. IL-1 activity of culture supernatants, collected 24 h after the addition of viral proteins, was evaluated by the standard IL-1 assay using C3H/HeJ thymocytes. Viral NA, but not HA, induced a significant increase of IL-1 activity (p less than 0.05) at dilutions ranging from 1:2 (about thirty-fold augmentation) to 1:256 (nine-fold augmentation) compared to control. The in vivo data showed that intraperitoneal administration of either glycoprotein (2 micrograms) alone did not increase the IL-1 activity; but a six-fold increase (p less than 0.05) of IL-1 activity was observed when the adherent macrophages prepared from NA-primed mice (24 h and 96 h postinoculation) were restimulated in vitro with NA. Similar experiments carried out with HA showed no increase in the IL-1 activity. These and other results suggest that influenza virus NA is superior to HA in stimulating some components of the nonspecific resistance mechanisms.