Elsevier

Cytokine

Volume 37, Issue 1, January 2007, Pages 14-21
Cytokine

The effect of compound nutrients on stress-induced changes in serum IL-2, IL-6 and TNF-α levels in rats

https://doi.org/10.1016/j.cyto.2007.02.009Get rights and content

Abstract

The effect of compound nutrients on serum concentrations of the cytokines, such as interleukin (IL)-2, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in immobilization and cold water-immersion stressed rat were investigated. Oral (gavage) administration of compound nutrients was found to attenuate the acute and chronic immobilization and cold water-immersion stress-induced increase in serum IL-6 level and decrease in IL-2 level. Compound nutrients exerted different effects on TNF-α level in two different models studied, with reduced serum TNF-α level in acute stress, while no significant effect in chronic stress. These results suggested that compound nutrients might be proposed as a possible candidate in the research or therapeutic modulation of stress-related disorders.

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)

  • J. Landeira-Fernandez

    Analysis of the cold-water restraint procedure in gastric ulceration and body temperature

    Physiol Behav

    (2004)
  • B.N. Hangalapura et al.

    Cold stress equally enhances in vivo pro-inflammatory cytokine gene expression in chicken lines divergently selected for antibody responses

    Dev Comp Immunol

    (2006)
  • P.H. Black

    The inflammatory response is an integral part of the stress response: implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X

    Brain Behav Immun

    (2003)
  • M. Maes et al.

    The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety

    Cytokine

    (1998)
  • M.Y. Engelsma et al.

    Neuroendocrine–immune interactions in fish: a role for interleukin-1

    Vet Immunol Immunopathol

    (2002)
  • E.N. Deliargyris et al.

    Sites of interleukin-6 release in patients with acute coronary syndromes and in patients with congestive heart failure

    Am J Cardiol

    (2000)
  • J.S. Yudkin et al.

    Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?

    Atherosclerosis

    (2000)
  • H. Nukina et al.

    Restraint stress elevates the plasma interleukin-6 levels in germ-free mice

    J Neuroimmunol

    (2001)
  • J.S. Gottdiener et al.

    Induction of silent myocardial ischemia with mental stress testing: relation to triggers of ischemia during daily life activities and to ischemic functional severity

    J Am Coll Cardiol

    (1994)
  • B. Shukitt-Hale et al.

    The effects of dietary antioxidants on psychomotor performance in aged mice

    Exp Gerontl

    (1999)
  • S.N. Meydani et al.

    Vitamin E supplementation suppresses prostaglandin E synthesis and enhances the immune response of aged mice

    Mech Ageing Dev

    (1986)
  • E.K. Boon-Niermeijer et al.

    Phyto-adaptogens protect against environmental stress-induced death of embryos from the freshwater snail Lymnaea stagnalis

    Phytomedicine

    (2000)
  • V. Darbinyan et al.

    Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty

    Phytomedicine

    (2000)
  • M. Ohsugi et al.

    Active-oxygen scavenging activity of traditional nourishing-tonic herbal medicines and active constituents of Rhodiola sacra

    J Ethnopharmacol

    (1999)
  • B. Dugue et al.

    Effects of psychological stress on plasma interleukins-1 beta and 6, C-reactive protein, tumour necrosis factor alpha, antidiuretic hormone and serum cortisol

    Scand J Clin Lab Invest

    (1993)
  • J.K. Kiecolt-Glaser et al.

    Chronic stress and age-related increases in the proinflammatory cytokine IL-6

    Proc Natl Acad Sci USA

    (2003)
  • V. Chesnokova et al.

    Minireview: neuro-immuno-endocrine modulation of the hypothalamic–pituitary–adrenal (HPA) axis by gp130 signaling molecules

    Endocrinology

    (2002)
  • B.N. Lambrecht

    Immunologists getting nervous: neuropeptides, dendritic cells and T cell activation

    Respir Res

    (2001)
  • T. Nishimura et al.

    A critical role for antigen-specific Th1 cells in acute liver injury in mice

    J Immunol

    (1999)
  • A.C. Mullen et al.

    Role of T-bet in commitment of TH1 cells before IL-12-dependent selection

    Science

    (2001)
  • J. Das et al.

    A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation

    Nat Immunol

    (2001)
  • T.R. Mosmann et al.

    Two types of murine helper T cell clone: I. Definition according to profiles of lymphokine activities and secreted proteins

    J Immunol

    (1986)
  • I.J. Elenkov

    Glucocorticoids and the Th1/Th2 balance

    Ann N Y Acad Sci

    (2004)
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