Increased serum levels of advanced glycation end products due to induced molting in hen layers trigger a proinflammatory response by peripheral blood leukocytes.

Induced molting (IM), a severe detriment to animal welfare, is still used in the poultry industry in some countries to increase or rejuvenate egg production and is responsible for several physiological perturbations, possibly including reactive oxidative stress, a form of metabolic stress. Because metabolic stress has been shown to induce a proinflammatory response involved in attempts to restore homeostasis, we hypothesized that similar responses followed IM. To confirm this hypothesis, we initially confirmed the establishment of oxidative stress during IM in 75-wk-old layers by demonstrating increased production of advanced glycation end products (AGE). Concomitant with increased oxidative metabolites, cellular stress was demonstrated in peripheral blood leukocytes (PBL) by increased levels of stress gene products (the glucocorticoid receptor, sirtuin-1, and heat shock protein 70 mRNA). Increased expression of stress proteins in PBL was followed by a proinflammatory response as demonstrated by increased levels of proinflammatory gene products (IL-6 and IL-1β mRNA); increased expression of these gene products was also demonstrated in direct response to AGE in vitro, thus establishing a direct link between oxidative and cellular stress. To establish a possible pathway for inducing a proinflammatory response by PBL, we showed that AGE increased a time dependent expression of galactin-3, Toll-like receptor-4, and nuclear factor - κB, all involved in the proinflammatory activation pathway. In vivo, AGE formed complexes with increased levels of circulating acute phase proteins (lysozyme and transferrin), products of a proinflammatory immune response, thereby demonstrating an effector response to cope with the consequences of oxidative stress. Thus, the harmful consequences of IM for animal welfare are extended here by demonstrating the activation of a resource-demanding proinflammatory response.