Changes in endocrine and immune responses of neonatal pigs exposed to a psychosocial stressor

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Abstract

The aim of the study was to determine the effects of a single social isolation (4 h) of piglets on immediate changes in stress hormones and immune responses at 7, 21 or 35 days of age. This social stressor caused an increase in plasma ACTH and cortisol concentrations and a decrease in plasma TNF-α. The percentage of CD8+ cells increased and the CD4+ cell percentage decreased, resulting in decreasing CD4+/CD8+ ratio. The observed changes were consistent for all days studied. Further, the isolation treatment resulted in diminished LPS-stimulated IL-1β and IL-10 production in whole-blood cultures. In isolated piglets, positive correlations were estimated between changes in percentage of CD8+ cells and cortisol, and negative ones between changes in plasma TNF-α and culture supernatant IL-1β with ACTH and cortisol. The data suggest that psychosocial stress in neonatal pigs induced immune alterations to maintain adaptive stability, but reflecting also negative emotions experienced by this treatment.

Introduction

Stress is generally defined as a state of altered homeostasis by an external or internal stimulus resulting in physiological changes, an active and adaptive process termed allostasis (McEwen, 1998). The response of the immune system to stress is one of the adaptive mechanisms that organisms have developed to cope with challenging situations. Although the stress response is an evolutionarily psychophysiological survival mechanism to maintain stability and health, an insufficient adaptation can lead to reduced immune competence and increased disease susceptibility (McEwen, 1998, Dhabhar, 2002).

It is well established in animal and human research that stress and stress hormones induce changes in numbers and proportions of blood leukocytes that act as a first line of defense against possible infection or injury (Dhabhar et al., 1996, Stefanski, 2000). Furthermore, acute stress has also been shown to affect mitogen-induced cell proliferation, natural killer cell cytotoxicity and circulating inflammatory factors (Stefanski and Engler, 1998, Hicks et al., 1998, Wrona et al., 2001, Steptoe et al., 2007). These immediate effects of stress upon immune function can be triggered by exposure to infectious microorganisms and also by non-infectious stressors (Sapolsky et al., 2000). Recently, it has been suggested that painful or threatening stimuli as well as social stress induced by isolation may also activate pathways underlying the acute phase response (Maier and Watkins, 1998, Hennessy et al., 2004). Even exposure to an open field has been found to elevate cytokine levels in rats (LeMay et al., 1990).

Further, it is known that the activation of hypothalamic-pituitary-adrenal (HPA) axis by stressful stimuli, resulting in release of glucocorticoids is a major modulator of immune responses (Sapolsky et al., 2000, Anisman et al., 2003). Glucocorticoids are widely regarded as being immunosuppressive and anti-inflammatory (McEwen et al., 1997, Franchimont, 2004). However, there is also evidence that acute stress levels of glucocorticoids can enhance T cell function (Dhabhar and McEwen, 1996), expression of acute-phase proteins (Jensen and Whitehead, 1998) and pro-inflammatory cell migration and cytokine production (Wiegers et al., 2005, Sorrells and Sapolsky, 2006).

Experiences during early postnatal life have been shown to play an important role for normal development of the brain, immune system and mechanisms of adaptation (Ader, 1983, Matteri et al., 1998, Coe and Laudenslager, 2007). Relating to piglets the first weeks of life constitute the most critical period, their immune competence undergoes dramatic development by exposure to natural or vaccine antigens (Becker and Misfeldt, 1993, Schwager and Schulze, 1997, Sinkora et al., 2002, Borghetti et al., 2006a, Borghetti et al., 2006b). In addition, there are numerous challenges within a domestic piglet’s environment such as housing conditions, handling by humans, abrupt weaning and the disruption of social relationships, that can evoke a stress response (Bianchi et al., 1999, Orgeur et al., 2001, Bolhuis et al., 2003, Davis et al., 2006). However, limited information exists how the immune system responds in neonatal piglets to cope with stressful situations. Thus, it is necessary to amplify our knowledge about the complexity of the relationship between stressful events and immunological functioning during the postnatal period. Moreover, there is growing interest in assessment of psychosocial stress in farm animals to improve our understanding of animals’ welfare, health and growth performance.

Maternal deprivation and social isolation is a well-recognized model of psychosocial stress not only in laboratory animals (Boccia et al., 1997, Blanchard et al., 2001) but also in sheep (Degabriele and Fell, 2001) and pigs (Herskin and Jensen, 2000, Kanitz et al., 2004) that robustly activates the release of glucocorticoids. Recent findings from our group indicate that repeated social isolation of neonatal pigs may cause changes in neuroendocrine and immune regulation and can modulate coping mechanisms against a later risk of infection (Kanitz et al., 2004, Tuchscherer et al., 2004, Tuchscherer et al., 2006). In addition, it is also known that the age of offspring may affect the intensity of separation stress (Weary et al., 1999, Newberry and Swanson, 2008).

Taking into account the developmental stage of neonatal immunity in pigs, the present study was designed to gain information on immediate changes of hormonal and immune responses in piglets of 3 age categories to an experimental psychosocial stress condition. Therefore, the plasma concentration of stress hormones and cytokines, the proportion of circulating lymphocyte subpopulations, the mitogen-induced T- and B-cell proliferation as well as the ex vivo activation of pro- and anti-inflammatory cytokine production were investigated in order to characterize the impact of a single social isolation treatment in suckling piglets on days 7, 21 and 35 of age.

Section snippets

Animals

Piglets were taken from eight German Landrace litters, born and raised under conventional management practices in the experimental pig unit of our institute. After birth the litter size was standardized to 10 piglets. Each piglet could be recognized by a tattoo number in the ear. All piglets received standard processing (tail docking, teeth grinding, oral iron supplementation, and male piglets were castrated) within the first 3 days of life from the same pig unit staff member. Piglets were

Baseline values before the experimental period

Baseline values (LS means and standard errors) of plasma ACTH, cortisol, TNF-α and IL-6 concentrations, peripheral blood mononuclear cells, proportions of lymphocyte subsets, lymphocyte stimulation indices in response to ConA and LPS as well as IL-1β and IL-10 concentrations in supernatants of whole blood cell culture after LPS stimulation are presented in Table 1. ANOVA indicated that all baseline values were mainly affected by age of piglets (F test, at least P < 0.05), whereas sex had no

Discussion

Although most components of the native and acquired immune systems in pigs are functional at birth, they are generally less efficient than in the adult, and active developmental changes in immune function occur during the neonatal period (Hammerberg et al., 1989, Matteri et al., 1998). In the present study, the percentages of CD8+ and CD4+CD8+ cells increased, whereas those of CD4+ cells tended to decrease during the first 5 weeks of life. This is further reflected in decreasing CD4+/CD8+ ratios

Conflict of interest statement

None declared.

Acknowledgements

The authors thank the staff of the Research Unit of Behavioural Physiology for their technical assistance. The study was supported by a grant from the German Research Foundation (KA 1266/4-1).

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