Eae

*For each immune challenge, animals were presented with two graduated tubes containing the sweet solution or water. Data represents the mean (+ S.E.M.) fluid consumption over a 24 hr period in non-deprived rats, following administration of LPS, IL-1(J, Mycoplasma fermentans or gpl20. Data for the acute immune challenges refcres to the consumption of a 10 mM saccharin solution by rats. Data for the EAE model refers to the consumption of a dilute sucrose solution by SJL mice over a period of 6 hr...

Increased IL1 Receptor Antagonist

Interleukin-1 receptor antagonist (IL-lra) competitively inhibits binding of IL-ip to its receptor.Three forms of IL-lra exist soluble IL-lra (sIL-lra) which is released extracellularly, and two forms of intracellular IL-lra (icIL-lra, types I and II) (Levine, Wu, & Shelhamer, 1997 Mantovani & Colotta, 1995). The affinity of IL-lra for the type I IL-1 receptor is approximately equal to that of IL-ip. However, due to the marked spare receptor effect for the IL-lp system, whereby very few...

References

R., Cohen, N., & Felten, D. (1991). Psychoneuroimmunology II. New York, Academic Press. Besedovsky, H. O. & del Rey, A. (1996). Immune-neuro-endocrine interactions Facts and hypotheses. Endocrine Reviews. 17. 64-102. Dunn, A.J. & Wang. J. (1995). Cytokine effects on CNS biogenic amines. Neuroimmunomodulation, 2, 319-328. Ericsson, A., Kovacs, J., & Sawchenko, P. E. (1994). A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on...

Summary And Conclusions

Our data indicate that the proinflammatory cytokine, IL-lalpha inhibits GR translocation and hormone-induced GR-mediated gene transcription, and, in conjunction with previous in vivo and in vitro studies, can be interpreted to suggest that cytokines have the capacity to contribute to glucocorticoid resistance and thus the pathophysiology of depression. In addition, data from our mouse viral studies in glucocorticoid deficient animals demonstrate that endogenous glucocorticoids modulate a...

Anxiety Behavioral Despair

Role of Glucocorticoids and the Glucocorticoid Receptor in Mediating Feedback Inhibition on IL-1 and CRH Potential Influence of Cytokines and Antidepressants. Stressors and immune activation secondary to inflammation and or infection serve as potent stimuli to corticotropin releasing factor (CRH) and interleukin (IL)-l respectively. Overexpression of these factors in turn can lead to behavioral disorders whose symptoms overlap and fall under the rubric of major depression....

Treatment Considerations

Accompanying the idea that impairment in GR number and or function as a consequence of genetic or environmental factors (e.g. immune processes) contributes to the pathophysiology of major depression, recent studies have suggested that a possible mechanism by which antidepressants treat depression is through effects on the GR. A number of animal studies have shown that in vivo treatment with a range of antidepressant agents including both tricyclic antidepressants and selective serotonin...

Consequences Of Glucocorticoid Resistance

In order to establish the potential relevance of glucocorticoid resistance to disease expression, it is important to establish the role of endogenous glucocorticoids in regulating cytokine and cellular responses during immune activation. To accomplish this task, we have recently examined the consequences of viral infection with MCMV in mice rendered glucocorticoid deficient by adrenalectomy. MCMV infection was chosen because this virus is associated with a surge in glucocorticoids which have...

Cytokines And Glucocorticoid Resistance

Given the potential role of glucocorticoid resistance in the pathophysiology of major depression, attention has focused on what factors might contribute to glucocorticoid resistance in depression. One interesting possibility involves the immune system. At least two disorders recently have been associated with glucocorticoid resistance in the context of immune activation, including steroid resistant asthma and infection with the human immunodeficiency virus (Miller, Pearce, Ruzek, & Biron, In...

Introduction

The concept of an inter-relationship between the psychological state of a depressed patient and the immune status can be traced back to Galen who, in 200 AD, suggested that melancholic women are more susceptible to breast cancer than sanguine women (Leonard, 1987). Over the past 15 years it has become apparent that the central nervous system (CNS) and the immune system are intimately connected and that a functional bidirectional communication exists between these systems (Ballieux, 1992)....

Effects Of Antidepressants On Depression Induced By Immune Activation

Antidepressants have been used successfully in treating depressive symptoms associated with various medical conditions (Katon & Sullivan, 1990). Both tricyclic antidepressants (TCAs) (Schiffer & Wineman, 1990) and selective serotonin reuptake inhibitors (SSRIs) (Scott, Nussbaum, McConnell, & Brill, 1995) have been used successfully in the treatment of depression associated with multiple sclerosis, stroke (Lauritzen, Bjerg Bendsen, Vilmar, Bjerg Bendsen, Lunde, & Bech, 1994),...

Behavioral Effects Of Infectious Diseases And Cytokine Administration In Animals

In animals, the association between acute illness and suppression of general activity, appetite and grooming has been reported by animal handlers and veterinarians long ago. Experimental studies, using systemic protozoan, bacterial or viral infections, provided more conclusive evidence for sickness-induced behavioral changes (Hart, 1988). In addition, exogenous administration of proinflammatory cytokines produces sickness behavior, whereas cytokine antagonists, as well as cytokine synthesis...

The Macrophage Theory Of Depression

Of all the endocrine changes that are reported to occur in stress and depression, Cortisol hypersecretion is the most frequently observed. Although hypercortisolaemia can arise as a consequence of an acute stressor, there is a qualitative difference between the circadian pattern of Cortisol secretion in the depressed patient and that observed following exposure to a stressful stimulus. Thus the nadir of the plasma Cortisol concentration occurs some 6 hours earlier in the depressed patient than...

Total Serum Protein And Electrophoretically Separated Protein Fractions In Major Depression And

Evidence for an apr that accompanies major depression was first reported by Maes et al. (1992a, b). The apr is reflected, too, in lowered levels of total serum protein (TSP) and changes in the major electrophoretically separated serum protein fractions. Several investigators (e.g. Schwartz et al., 1990 Joyce et al., 1992 Song et al., 1994a Maes et al., 1991, 1995b) reported lowered levels of serum albumin (Alb) in major depressed patients suffering major depression compared to normal controls....

Major Depression And Activation Of The Inflammatory Response System

Clinical Research Center for Mental Health (CRC-MH) Antwerp, Belgium IRCCS, Istituto Fatebenefratelli, Brescia, Italy, and Department of Psychiatry, Vanderbilt University, Nashville Contemporary models of major depression emphasize the role of hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity and of dysfunctions in the turnover of serotonin (5-HT) or catecholamines in the etiopathogenesis of major depression. Contemporary models of major depression do not incorporate the effects of the...

Info

Effect of vaccination with live-attenuated rubella virus on depression scores, measured by the Children Depression Inventory in 12-years old girls with low socioeconomic status. Monson, Sobol, Federman, & Leighton, 1991). This vulnerability may be associated with several characteristics of low SES, including higher incidence of stressful life events, and fewer sources of social support (Adler, Boyce, Chesney, Cohen, Folkman, Khan, & Syme, 1994 Anderson & Armstead, 1995...

Antibodies Against Serotonin And Gangliosides In Major Depression And

Several authors have show the occurrence of antinuclear, antiphospholipid and antiserotonin, antihistone, antibodies in depression Villemain, 1988 Irwin et al., 1990 Maes et al., 1991 Schott et al., 1992 . Some autoimmune disorders have been related to the induction of antihormone and anti-receptor antibodies Cohen and Cook, 1986 . We have recently reported the occurrence of antibodies against serotonin and gangliosides in major depressed patients Sluzewska et al., 1997d . Antibodies against...

Depressionassociated Alterations In The Hpa System

Functional changes often referred to as dysregulations of the HPA system have been extensively documented in patients with depression Akil amp Ines Morano, 1995 Post amp Weiss, 1995 Holsboer amp Barden, 1996 . These include increased episodes of ACTH and Cortisol secretion, elevated mean Cortisol levels in the blood and increased free urinary Cortisol levels. Various observations from both clinical and experimental animal studies support a causal link between dysregulation of the HPA system and...

Immune Alterations In Depressed Patients

Until now, very few investigations have been carried out to assess the effects of antidepressant medications on the immune alterations associated with depression and more specifically to assess whether antidepressants normalize immunity and or abrogate the production and release of proinflammatory cytokines. In order to answer these questions, it is first necessary to depict the immune status that is usually observed during depression. The immune parameters studied in depressed patients usually...