Interferon action on avian viruses. I. Oral administration of chicken interferon-alpha ameliorates Newcastle disease.

881 EVID EN CE IS M OU N TIN G that interferon (IFN) administe red orally to mammals in low doses mirrors to varying degrees the effects of IFN administered parentally in high doses as antiviral (1– 7) or antitum or(6– 9) agents, and as immunomodulators. (6 ,1 0,11) This evidence, coupled with the availability of a type I recombinan t chicken interferon (rChIFNa ),(12 ,28 ) and the possibility of administering avian IFN under conditions that accomm odate the economics of poultry production , provide the rationale for testing the efficacy of avian IFN delivered orally as an antiviral agent. To this end, we present the results of a study that demonstrates rChIFNa administered to chickens in drinking water ameliorate s the effects of Newcastle disease brought on by challenge with Newcastle disease virus (NDV). The rChIFNa was prepared from transfected COS cells constitutively expressing glycosylated ChIFNa ,(1 2) and was administered orally to groups, usually of 16, newly hatched, specific pathogen-free chickens, obtained from SPAFAS, Inc (Storrs, CT). The chickens had not been vaccinated against NDV. Chickens were started at one day of age on IFN-containing drinking water provided ad libitum in conventional galvanized zinc troughs. IFN-drinking water was changed daily and used continuously throughout the experim ent. The design of the metal brooders used inevitably led to the newly hatched chickens soiling the IFN-drinking water. This necessitated filter sterilization of the water before assay to determine the effective half-life of the rChIFNa . These “field” conditions produced an effective T1/2 > 32 h at room temperature (RT). When kept sterile and under laboratory test conditions, the T1/2 of rChIFNa in tap water at RT was extended to about 5 days. The dose of IFN imbibed during a 24-h period was estimated by taking into consideration the starting concentration of IFN, its T1/2, and the average volume of water consum ed. On the basis of results from six independent experiments where the drinking water was formulated to contain variously 10, 100, 500, 1,000, or 2,000 U/ml of rChIFNa , the total dose of IFN administered orally was about 150, 1,500, 7,500, 15,000 and 30,000 Units(13)/bird per 24 h, respectively. Groups of chicks without IFN in the drinking water were included in each experiment as virus controls. In five of the six experiments, uninfected chicks were housed separately and maintained without IFN in their drinking water as controls on both IFN and virus. The use of a water system with nipple drinkers should obviate contamination of the drinking water that contains IFN and extend its T1/2. The common practice of using nonfat dried milk added to the water to neutralize chlorine should further stabilize the ChIFN,(14 ) providing a practical and economical way to deliver IFN in poultry. Challenge with NDV was carried out 1 day after starting the chicks on IFN-containin g water, i.e., at 2 days of age. We have yet to determ ine whether additional time of pretreatment with IFN-water would be more efficacious. All birds were infected intraocularly (0.05 ml/eye) with 5 to 10 3 105 EID50 doses of the LaSota strain of NDV. This is a vaccine strain that produces mild symptoms and pathology of Newcastle disease. Thus, rales (a rattling sound in the throat), a characteristic symptom of respiratory stress brought on by Newcastle disease, was quite apparent in virus controls by day 3 post-infection and continued to increase in severity for several days thereafter. At the two highest doses of IFN used (1,000 and 2,000 U/ml water), the onset of rales was delayed and decreased in its severity. In one experiment, virus-infected birds and those fed with low doses of IFN in their drinking water (10 and 100 U/ml) developed a lethargic state by day 7 post-infection. In contrast, all birds that received 1,000 U/ml IFN-containing water and had been challenged with NDV at the same time, were alert and frisky throughout the 12-day course of the experiment. Figure 1 shows the weight of chickens 12 days after imbibing IFN-containing water. This corresponded to day 11 postinfection. For the IFN concentration shown, the mean and standard deviation of the weight of birds in grams for each treatm ent group was as follows: 0 (75.9 6 5.9), 10 (76.4 6 7.4), 100 (76.2 6 12.2), 1,000 (82.2 6 19.0). Although the differences in the mean weights are not considered significant, there was a trend toward a broader distribution of weights with increasing dose of IFN. Thus, the group of 16 birds on drinking water that contained 1,000 U/ml IFN contained 3 members that weighed over 100 grams, whereas none of the other groups contained