|Carroll, Jeffery - Jeff Carroll|
|WELSH JR, TOM|
Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2009
Publication Date: 10/10/2009
Citation: Williams, P., Carroll, J.A., Welsh Jr, T., Collier, C., Laurenz, J. 2009. Temporal pattern and effect of sex on lipopolysaccharide-induced stress hormone and cytokine response in pigs. Domestic Animal Endocrinology. 37:139-147.
Interpretive Summary: Currently, little is known about the interactions between sympathetic nervous system and the immune response following an immune challenge in domestic animals. Animal response to the stress of disease can greatly affect the extent of the associated morbidity and significantly impact animal health and subsequent economic losses. To address this issue, scientists within the ARS' Livestock Issues Research Unit participated in a collaborative research study with scientists from Texas A&M University at Kingsville and College Station to establish the temporal pattern of the catecholamine response following immune activation by an endotoxin challenge in pigs, and to assess the relationship between the catecholamine, cortisol, and immune responses following this immune challenge. For this study, 40 nursery pigs were obtained at 21 to 28 days of age and transferred to the Livestock Issues Research Unit nursery building where they were weightd, assigned to individual pens, and allowed ad libitum access to food and water. All 40 pigs were non-surgically fitted with an indwelling jugular catheter for the collection of blood samples at 30-minute intervals for 1 hour prior to and 6 hours post-endotoxin infusion with the exception of the 15-minute intervals between 0 and 1 hour for analysis of catecholamines and a 24 hour sample for analysis of acute phase proteins. Although other studies with pigs have not specifically reported the relationhip among inflammatory cytokine production following endotoxin infusion and the stress response, the relationships reported in this study are consistent with the ability of endotoxin to cause activation and translocation of the transcription factor NF-kB which is known to induce the transcription of a wide array of proinflammatory cytokine genes. Furthermore, this study indicates gender-specific differences in immune and stress respone to antigenic challenges. Therefore, further studies could account for sex-based differences and provide novel new insight into the reasons why gender influences the cumulative immune and stress responses to pathogenic challenge. The present results support the hypothesis that LPS challenge triggers a synergistic cascade of stress- and immune-related hormones resulting in a repartitioning of immune cells. Moreover, an unexpected observance is that immune and stress reactions are influenced by gender. To our knowledge, this is the first study to report the catecholamine response in pigs following a LPS challenge. Results reported within this manuscript will be of specific interest to scientists in academia, industry, and governmental agencies working in the area of stress and immunology.
Technical Abstract: The temporal pattern and gender effect on immune and stress hormone responses to a lipopolysaccharide (LPS) challenge was assessed using a pig model. Secretion of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1) beta and IL-6 increased (P < 0.05) in a time-dependent manner following LPS infusion. There were also time dependent increases (P<0.05) in secretion of the stress-related hormones cortisol, epinephrine (E), and norepinephrine (NE) following LPS with peak concentrations attained within 30 minutes. The duration of the TNF-alpha and IL-1 beta responses were both positively associated with the duration of cortisol response following LPS, while serum IL-1 beta and IL-6 were positively associated with the duration of E and NE responses following LPS. Acute phase protein production was also time-dependently increased (P<0.05) following LPS. The concentration of immune cells in circulation was decreased (P<0.05) at 5.5 hours post-LPS and negatively correlated with proinflammatory cytokine production. By 24 hours post-LPS, immune cell counts increased (P<0.05) and were positively associated with both proinflammatory cytokine and stress hormone production (P<0.05). Interestingly, the magnitude of proinflammatory cytokine response following LPS was effected by sex classification (P<0.05), however the duration of elevated cytokine concentrations was not (P>0.05). The magnitude of the NE response, but not of the E and cortisol response, to LPS was influenced by sex (P<0.05). Similar to the proinflammatory cytokines, the duration of exposure to the stress hormones following LPS was not influenced by sex (P>0.05). The production of serum amyloid A (SAA) was influenced by sex (P<0.05) with barrows producing more SAA at 24 hours post LPS than gilts.