The Effect of 5-Fluorouracil Treatment of Chicks: A Cell Depletion Model for the Study of Avian Polymorphonuclear Leukocytes and Natural Host Defenses

Abstract

Two-week-old Leghorn chicks injected intravenously with 5-fluorouracil (5-FU) were found to have a three- to fivefold reduction (P < .05) in circulating polymorphonuclear leukocytes (PMN) 5 to 10 days later. The reduction in PMN was dose-dependent with a dosage of 200 mg/kg body weight of 5-FU, causing suppression of PMN to almost undetectable levels. Increasing the dosage of 5-FU to 400 mg/kg had no further effect on reducing the number of PMN in the circulation nor were overt clinical signs of toxicity observed. Single per os administration of 10(6) viable Salmonella enteritidis (SE) to individual groups of chicks treated or not treated with 5-FU at 2, 4, 6, 8, 10, or 12 days postinjection resulted in a two- to sixfold increase in the incidence of SE organ invasion (liver and spleen) beginning on Day 4 postinjection and continuing through Day 12 postinjection. The greatest increase in organ invasion occurred on Days 8 through 10 postinjection and was inversely proportional to the greatest reduction in the number of circulating PMN. Using 5-FU, a granulocytopenic chicken model was developed that can be used to study the defensive role of avian heterophils against infectious agents. The results from these preliminary experiments indicate that PMN play a significant role in reducing organ invasion by SE in Leghorn chicks.

Impact of heterophil granulocyte depletion caused by 5-fluorouracil on infectious bursal disease virus infection in specific pathogen free chickens

“…However, the number of heterophil granulocytes was drastically reduced in both treated groups 7 and 8 days after 5-FU treatment, 2 and 3 days after virus inoculation, when viraemia was expected. The results of the blood cell counts were too few to be statistically evaluated, but the effect of 5-FU on blood cells seemed already discussed in detail by Kogut et al (1993) and Bojesen et al (2004). The histological studies of bursa tissues confirmed the results of lymphocyte counts, revealing cellular depletion 5 days after 5-FU treatment.…”

“…The effect of 5-FU is related to its replacement of uracil in RNA (Ardalan & Glazer, 1981). A dose of 200 mg/kg was injected once into the vena ulnaris (Kogut et al ., 1993). Sterile saline was used as placebo.…”

“…A model for heterophil depletion of chickens by treatment with the cytostatic drug 5-flurouracil (5-FU) has been described (Kogut et al ., 1993) and used for investigation of the influence of heterophil granulocytes on bacterial (Bojesen et al ., 2004) andviral (Raj et al ., 1997) infections in chickens. In a previous, unpublished experiment, chickens treated with the recommended dose of 5-fluorouracil (5-FU) and subsequently infected with IBDV showed mild clinical symptoms, but survived the infection.…”

Salmonella infections: immune and non-immune protection with vaccines

“…Another result underlining the importance of chicken heterophils in protection against Salmonella organ invasion was the finding that intraperitoneal administration of S. Enteritidis-immune lymphokines (SE-ILK) to 18-week old chickens protected the animals from organ invasion by S. Enteritidis (Hargis et al, 1999;Tellez et al, 1993). SE-ILK are soluble products produced by Tlymphocytes, derived from S. Enteritidis-immune hens, cultured in the presence of concanavalin A. Intraperitoneal administration of SE-ILK in chickens resulted in a dramatic increase in the number of heterophilic granulocytes into the peritoneum without changing the numbers of other leukocytes and administration in ovo protected young chicks against organ invasion by Salmonella (Kogut et al, 1995a(Kogut et al, , 1995b.…”

“…Granulocytopoenic (heterophil-depleted) chickens are much more susceptible to S. Enteritidis organ invasion, with the increase in bacterial number in the internal organs being proportionally related to the decrease in number of circulating PMNs (Kogut et al, 1993;Ibid 1994). Another result underlining the importance of chicken heterophils in protection against Salmonella organ invasion was the finding that intraperitoneal administration of S. Enteritidis-immune lymphokines (SE-ILK) to 18-week old chickens protected the animals from organ invasion by S. Enteritidis (Hargis et al, 1999;Tellez et al, 1993).…”