Effects of postnatal social isolation on hormonal and immune responses of pigs to an acute endotoxin challenge.
ABSTRACT Social stress during early postnatal life often results in long-term effects on neuroendocrine and immune adaptation mechanisms. Therefore, the aim of the present study was to determine the influence of a 2-h daily social isolation from Day 3 to Day 11 on the acute and long-term proinflammatory and neuroendocrine responses of piglets challenged with the bacterial endotoxin lipopolysaccharide (LPS; 100 microg/kg body weight). Peripheral LPS administration significantly increased plasma concentrations of tumor necrosis factor-alpha (TNF-alpha), ACTH and cortisol in isolated and control pigs. However, the activity of the hypothalamic-pituitary-adrenal (HPA) axis after LPS stimulation was not significantly affected by isolation treatment, whereas the prior social isolation diminished the plasma TNF-alpha response to LPS 1 day as well as 45 days after the isolation period. The hippocampal TNF-alpha concentration in response to LPS was also reduced in priorly isolated pigs compared to control animals. Furthermore, the significant increase of TNF-alpha in the spleen caused by LPS was associated with a dramatic decrease in glucocorticoid receptor (GR) binding. The GR binding in hippocampus was increased in isolated pigs and was significantly decreased after LPS injection. In addition, the repeated isolation stressor was shown to increase hippocampal levels of interleukin-1beta (IL-1beta). The present results indicate that repeated social isolation of neonatal pigs may cause long-term effects on proinflammatory regulation at the periphery and in the brain following immune challenge with particular importance of TNF-alpha in mediating these interactions.
- Advances in The Study of Behavior - ADVAN STUDY BEHAV. 01/1998; 27:371-403.
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ABSTRACT: The immune system and the central nervous system form a bi-directional communication network. The critical roles of pro-inflammatory cytokines in both the periphery and the nervous system are discussed. In the periphery, these cytokines initiate the processes that signal the brain that immune activation has occurred, and communicate this information over both neural and blood-borne routes. The arrival of these signals in the central nervous system induces a neural cascade that includes the de novo induction of pro-inflammatory cytokines. The functions of these cytokines in the nervous system are discussed, and it is argued that they play a key role in regulating the neural control of immune processes in the periphery. In addition, it is argued that these cytokines play a variety of other roles, and some implications of the cytokine network for understanding stress, behavior, sensory processing, mood, and cognition are described. The overall argument is that because brain-mediated host defense involves behavioral, sensory, mood, and cognitive alterations, immune activation, and immune products such as the cytokines can have a pervasive effect on these functions. Finally, these phenomena are placed in an evolutionary perspective.Brain Behavior and Immunity 05/2003; 17(2):69-85. · 5.61 Impact Factor
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ABSTRACT: The subject of neuroinflammation is reviewed. In response to psychological stress or certain physical stressors, an inflammatory process may occur by release of neuropeptides, especially Substance P (SP), or other inflammatory mediators, from sensory nerves and the activation of mast cells or other inflammatory cells. Central neuropeptides, particularly corticosteroid releasing factor (CRF), and perhaps SP as well, initiate a systemic stress response by activation of neuroendocrinological pathways such as the sympathetic nervous system, hypothalamic pituitary axis, and the renin angiotensin system, with the release of the stress hormones (i.e., catecholamines, corticosteroids, growth hormone, glucagons, and renin). These, together with cytokines induced by stress, initiate the acute phase response (APR) and the induction of acute phase proteins, essential mediators of inflammation. Central nervous system norepinephrine may also induce the APR perhaps by macrophage activation and cytokine release. The increase in lipids with stress may also be a factor in macrophage activation, as may lipopolysaccharide which, I postulate, induces cytokines from hepatic Kupffer cells, subsequent to an enhanced absorption from the gastrointestinal tract during psychologic stress. The brain may initiate or inhibit the inflammatory process. The inflammatory response is contained within the psychological stress response which evolved later. Moreover, the same neuropeptides (i.e., CRF and possibly SP as well) mediate both stress and inflammation. Cytokines evoked by either a stress or inflammatory response may utilize similar somatosensory pathways to signal the brain. Other instances whereby stress may induce inflammatory changes are reviewed. I postulate that repeated episodes of acute or chronic psychogenic stress may produce chronic inflammatory changes which may result in atherosclerosis in the arteries or chronic inflammatory changes in other organs as well.Brain Behavior and Immunity 01/2003; 16(6):622-53. · 5.61 Impact Factor