ABSTRACI'. We studied the effects of combined administration of human immunoglobulin (IVIG) and ribavirin aerosol on respiratory syncytial virus (RSV) infection in cotton rats (Sigmodon hispidus). Cotton rats assigned to receive combined therapy were administered Gamimune, a preparation of purified IVIG with a high titer of anti-RSV neutralizing activity, intraperitoneally 24 h prior to intranasal RSV challenge and then treated with ribavirin aerosol 3 days after challenge. Lung viral titers from these cotton rats (geometric mean titers [GMT] loglo = 0.15 f 0.5) were lower than titers from untreated animals (GMT, loglo = 3.7 f 0.6) and animals treated with either IVIG alone (GMT, loglo = 1.8 f 0.9) or ribavirin alone (GMT, loglo = 1.9 f 1.1). Only one of 12 cotton rats treated with both IVIG and ribavirin had a demonstrable titer of virus after RSV challenge. When IVIG administration was delayed until day 3 after virus challenge, lung viral titers were still lowest in animals receiving both IVIG and ribavirin. In comparison, there was no additive antiviral effect between IVIG and ribavirin against RSV infections of HEp-2 cells in vitro. Pathologic changes on histologic examination of pulmonary tissues from animals challenged with RSV were least prominent in animals treated with both IVIG and ribavirin. Despite the apparent absence of in vitro additive antiviral effect, combined use of IVIG and ribavirin was more efficacious against RSV infection in the cotton rat than use of either agent alone. (Pediatr Res 21: 270-274, 1987) Abbreviations RSV, respiratory syncytial virus IVIG, human immunoglobulin TCID50, tissue culture infections doses MEM, minimal essential medium SFU, syncytia forming units PBS, phosphate-buffered saline GMT, geometric mean titers serious RSV disease may require treatment with combinations of currently available therapeutic agents.Previous studies have shown that parenteral inoculation of IVIG containing a high titer of anti-RSV neutralizing activity can provide significant protection in the cotton rat against RSV infection, (3) and significantly reduce the amount of virus shed from the airways of RSV infected owl monkeys (4). Ribavirin( 1 -0-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a synthetic nucleoside that possesses inhibitory activity against RSV in vitro, has been shown to reduce the amount of RSV in lung tissue of experimentally infected cotton rats (6) and appears to exert a beneficial effect on the course of human RSV infection (7-9). The present study evaluated the combined effect of IVIG and ribavirin on the quantity of RSV contained in lungs of experimentally infected cotton rats and the effect of this combination on histopathologic evidence of infection. METHODSAnimals. Cotton rats (Sigmodon hispidus) used in these studies were derived from two pairs of animals obtained from the Small Animal Section, Veterinary Resources Branch, Division of Research Services, National Institutes of Health. Test animals were 2-3 wk old at the start of each experiment. All animals were m...

The effects of influenza A/Hong Kong/68 (H3N2) virus infection on clearance of bacteria (Staphylococcus aureus or Serratia marcescens) from lungs of young adult (8-week-old) and aged (2-year-old) CBA/2N mice were studied. No consistent differences in pulmonary bacterial clearance were observed in uninfected animals of either age group. However, both young and aged virus-infected mice consistently exhibited significantly reduced ability to clear challenge bacteria from their lungs compared to age-matched nonvirus-infected controls; this deficit was markedly more pronounced in virus-infected aged mice. The extra deficit seen in virus-infected aged animals did not correlate with pulmonary virus or interferon titers, or with severity of pulmonary histopathology. Moreover, the phagocytic and bactericidal activities of pulmonary macrophages and polymorphonuclear neutrophiles from virus-infected young and aged mice were comparable.