The effect of compound nutrients on stress-induced changes in serum IL-2, IL-6 and TNF-α levels in rats
Introduction
Psychological and physical stress cause stress responses comprising neuronal, endocrine and immune reactions, which could lead to interference of host defenses [1], [2]. Modulation of the immune response is mediated by a complex network of signals that function in bi-directional communication among the nervous, endocrine and immune systems. The interaction, coordination and communication among nervous, endocrine and immune systems are mediated by common receptors to neurotransmitters, hormones and cytokines [3], [4], [5]. Stress-induced activation of the sympathetic-adrenal medulla and the hypothalamic–pituitary–adrenal (HPA) axis stimulates secretion of catecholamine (noradrenalin and adrenalin) and glucocorticoid, which are capable of modulating immune cells and further modulating cytokine production [6], [7], [8].
Cytokines may act as classic endocrine secretion. T helper 1 (Th1) and T helper 2 (Th2) cells represent two subpopulations of CD4+ T cells, which can be differentiated by their cytokine profiles, and it is now recognized that the Th1/Th2 balance is important for immunoregulation [9], [10]. Th1 cells produce interferon-γ (IFN-γ) and IL-2, which induce differentiation of CD4+ T cells to Th1 cells and inhibit the proliferation of Th2 cells. In contrast, Th2 cells secrete interleukin-4 (IL-4), IL-6 and IL-10, which induce differentiation of Th2 cells and inhibit Th1 cells. Both Th1 and Th2 cells secrete GM-CSF and TNF-α. Th1 activation contributes to cell-mediated immunity whereas Th2 activation favors the humoral immune response [11], [12], [13]. High concentrations of glucocorticoids stimulate the Th2 response and inhibit the Th1 response, and stress induces dysregulation of the Th1/Th2 cytokine profile [14]. Conditions associated with significant changes in glucocorticoid concentration, such as the introduction of acute or chronic stress, might affect the susceptibility or course of infection by modulating the Th1/Th2 balance [15], [16]. Among these cytokines tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 belong to proinflammatory cytokines, which are pleiotropic molecules produced by a variety of peripheral cell types as well as those cells in the central nervous system (CNS). These mediators are often associated with host defense and, as such, the production and release of proinflammatory cytokines are increased by infectious and inflammatory stimuli. Proinflammatory cytokines, therefore, play a critical role in several components of host defense, including CNS-orchestrated events. As proinflammatory cytokines often perform redundant functions, it is important to examine multiple cytokines in response to a given stressor to obtain an understanding of the role of proinflammatory cytokines in the behavioral and physiological response to stressor exposure. Therefore, our current experiment selected three cytokines as study target, including IL-2, IL-6 and TNF-α, to observe the changes of these cytokines in response to stress and to determine the effect of compound nutrients on these changes. Our current study focused on the changes of several cytokines in stress and the effect of intervention on these cytokines.
Many studies indicate that acute or chronic stress induces immunomodulatory effects in animal models as well as in humans [7]. Stress affects various aspects of immune function, depending on the nature and duration of the stress [17]. Nutrition status has a crucial effect on human health of physiology and psychology, which can help people adapt themselves to environment. Especially some micronutrients are neurotransmitters of central nervous system or those pro-substance, and have an important role in course of accommodating mentality and behavior. Supplementation with compound micronutrients has been shown to be beneficial in improving the stress adapting ability and in attenuating the stress-induced injuries in rats [18], [19]. And some reports have shown that herb extract and its components improve the lesions evoked by stress. Ginseng saponins have been proposed as a possible candidate in the laboratory research or therapeutic modulation of stress-induced disorders for their inhibitory effect on the level of stress-induced IL-6 in mice [20], [21], [22]. Therefore the efficacy of nutritional agents and plants as countermeasures for stress immunoregulation has gained considerable research attention [23]. The aim of the present study is to investigate the effect of our compound nutrients on cytokines such as IL-2, TNF-α and IL-6 in immobilized and cold water-immersed stress rat.
Section snippets
Animal
Adult male Sprague–Dawley rats weighing 180–200 g, supplied by the Animal Center of Fourth Military Medical University (Xi’an, China), were used for all the experiments. One day prior to the experiment, the rats caged in groups of five were allowed to be acclimatized to the condition of a quiet laboratory room overnight. The animals were housed five per cage in a room maintained at 22 ± 1 °C with an alternating 12 h light–dark cycle. Food and water were freely available. Animal protocol was approved
Effect of compound nutrients on the stress-induced serum IL-6 level
It has been reported that stress can cause an elevation of serum IL-6 level. In order to investigate the effect of orally administrated compound nutrients on serum IL-6 in immobilization and cold water-immersed stress rat, we first observed the effect of compound nutrients on acute stress. As shown in Fig. 1a, the serum IL-6 level significantly increased after immobilization and cold water-immersed stress in the group of the vehicle-treated rat. Compound nutrients (340.56 mg/ml, 3 ml/d/rat)
Discussion
Cytokines play a key role in bidirectional communication between the neuroendocrine and immune systems. The interplay between hormones and cytokines during thermal stress may influence immune homeostasis in response to environmental challenges [28]. Rhind SG found that cold stress enhanced IL-6, IL-2 and TNF-α cytokine levels in human. Cold stress did not have a significant effect on IL-1β cytokine levels in man, while in mice, cold exposure enhanced IL-1 cytokine levels [29], [30]. And many
Acknowledgments
This work was supported by grant (05XJM002) from the Fourth Military Medical University, and grants (01MB129, 06MA203 and 06Z047) from the Department of Health, General Department of Logistic, PLA and a grant (No. 30370580) from National Natural Science Foundation, China.
References (66)
The syntax of immune–neuroendocrine communication
Immunol Today
(1994)- et al.
Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic–pituitary–adrenal revolving axis
J Neuroimmunol
(2002) - et al.
How stress influences the immune response
Trends Immunol
(2003) - et al.
A role of the adrenal gland in stress-induced up-regulation of cytokines in plasma
J Neuroimmunol
(2006) - et al.
Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases
Immunol Today
(1995) - et al.
A novel transcription factor, T-bet, directs Th1 lineage commitment
Cell
(2000) - et al.
Dysregulation of the Th1/Th2 cytokine profile is associated with immunosuppression induced by hypothalamic–pituitary–adrenal axis activation in mice
Int Immunopharmacol
(2006) - et al.
The effect of Eleutherococcus senticosus and Pena ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes
Life Sci
(2001) - et al.
Anti-stress effects of Ginkgo biloba and Panax ginseng: a comparative study
J Pharmacol Sci
(2003) - et al.
The inhibitory effect of ginseng saponins on the stress-induced plasma interleukin-6 level in mice
Neurosci Lett
(2003)