Developmental windows of differential lead-induced immunotoxicity in chickens

The developing immune system of rodents has been shown to exhibit increased sensitivity to lead-induced immunotoxicity compared with that of adults. H owever, little is known about potential windows of increased vulnerability during discrete periods of embryonic development. To investigate differenti al embryonic sensitivity to lead-induced immunotoxicity, sublethal doses of lead ranging from 5 to 400 mug/egg were introduced into fertilized Cornell K Strain White Leghorn chicken eggs via the air sac at one of four differe nt stages of embryonic development (5, 7, 9, and 12 days of incubation, des ignated as E5, E7, E9, and E12, respectively). Lead levels of blood and bon e were determined at hatching and lead-induced immunotoxicity was evaluated in 5-6 week old young chickens using a delayed-type hypersensitivity (DTH) reaction against bovine serum albumin (BSA), macrophage production of nitr ic oxide, and interferon-gamma (IFN-gamma) production by splenic lymphocyte s as immune indicators. Splenic lymphocyte production of IFN-gamma was sign ificantly suppressed (measured for E7 and E9 exposures only, P < 0.05 among lead treated groups when compared with controls. Macrophage production of nitric oxide (measured as nitrite production) was significantly depressed ( P < 0.05) following E5, E7, and E9 lead exposures but not following E12 lea d exposure. In contrast with this pattern, DTH function was unaltered follo wing the E5, E7, and E9 exposures, but was significantly depressed (P < 0.0 5) after E12 exposure to lead. Since the same lead dose (200 <mu>g/egg) giv en at E9 and E12 produced the same blood and bone lead levels and resulted in a different outcome regarding DTH function, the capacity of lead to infl uence DTH function appeared to emerge between days 9 and 12 of in ovo devel opment. Based on these results, it is hypothesized that lead exposure durin g different windows of embryonic development is likely to result in differe nt immunotoxic outcomes in the juvenile. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.