Cytokines as mediators of depression: What can we learn from animal studies?

被引:339
作者
Dunn, AJ
Swiergiel, AH
de Beaurepaire, R
机构
[1] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol, Shreveport, LA 71130 USA
[2] Polish Acad Sci, Inst Genet & Anim Breeding, Jastrzebiec, Poland
[3] Hop Paul Guiraud, Villejuif, France
[4] INSERM, Creteil, France
关键词
cytokines; depression; interleukins-1; interferon; norepinephrine; serotonin; HPA Axis; sickness behavior; animal models;
D O I
10.1016/j.neubiorev.2005.03.023
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
It has recently been postulated that cytokines may cause depressive illness in man. This hypothesis is based on the following observations: 1. Treatment of patients with cytokines can produce symptoms of depression; 2. Activation of the immune system is observed in many depressed patients; 3. Depression occurs more frequently in those with medical disorders associated with immune dysfunction; 4. Activation of the immune system, and administration of endotoxin (LPS) or interleukin-1 (IL-1) to animals induces sickness behavior, which resembles depression, and chronic treatment with antidepressants has been shown to inhibit sickness behavior induced by LPS; 5. Several cytokines can activate the hypothalamo-pituitary-adrenocortical axis (HPAA), which is commonly activated in depressed patients; 6. Some cytokines activates cerebral noradrenergic systems, also commonly observed in depressed patients; 7. Some cytokines activate brain serotonergic systems, which have been implicated in major depressive illness and its treatment. The evidence for each of these tenets is reviewed and evaluated along with the effects of cytokines in classical animal tests of depression. Although certain sickness behaviors resemble the symptoms of depression, they are not identical and each has distinct features. Thus the value of sickness behavior as an animal model of major depressive disorder is limited, so that care should be taken in extrapolating results from the model to the human disorder. Nevertheless, the model may provide insight into the etiology and the mechanisms underlying some symptoms of major depressive disorder. It is concluded that immune activation and cytokines may be involved in depressive symptoms in some patients. However, cytokines do not appear to be essential mediators of depressive illness. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:891 / 909
页数:19
相关论文
共 193 条
[51]   The role of cyclooxygenases in endotoxin- and interleukin-1-induced hypophagia [J].
Dunn, AJ ;
Swiergiel, AH .
BRAIN BEHAVIOR AND IMMUNITY, 2000, 14 (03) :141-152
[52]  
Dunn AJ, 2005, TEC BEHAV N, V15, P157
[53]   THE ROLE OF INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR-ALPHA IN THE NEUROCHEMICAL AND NEUROENDOCRINE RESPONSES TO ENDOTOXIN [J].
DUNN, AJ .
BRAIN RESEARCH BULLETIN, 1992, 29 (06) :807-812
[54]   The reductions in sweetened milk intake induced by interleukin-1 and endotoxin are not prevented by chronic antidepressant treatment [J].
Dunn, AJ ;
Swiergiel, AH .
NEUROIMMUNOMODULATION, 2001, 9 (03) :163-169
[55]   ROLE OF CYTOKINES IN INFECTION-INDUCED STRESS [J].
DUNN, AJ .
CORTICOTROPIN-RELEASING FACTOR AND CYTOKINES: ROLE IN THE STRESS RESPONSE: HANS SELYE SYMPOSIUM ON NEUROENDOCRINOLOGY AND STRESS, 1993, 697 :189-202
[56]   THE ROLE OF CYCLOOXYGENASE AND LIPOXYGENASE IN THE INTERLEUKIN-1-INDUCED ACTIVATION OF THE HPA AXIS - DEPENDENCE ON THE ROUTE OF INJECTION [J].
DUNN, AJ ;
CHULUYAN, HE .
LIFE SCIENCES, 1992, 51 (03) :219-225
[58]  
DUNN AJ, UNPUB
[59]   TYPE-1 INTERLEUKIN-1 RECEPTOR IN THE RAT-BRAIN - DISTRIBUTION, REGULATION, AND RELATIONSHIP TO SITES OF IL-1-INDUCED CELLULAR ACTIVATION [J].
ERICSSON, A ;
LIU, C ;
HART, RP ;
SAWCHENKO, PE .
JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 361 (04) :681-698
[60]   Molecular mechanisms of endotoxin tolerance [J].
Fan, HK ;
Cook, JA .
JOURNAL OF ENDOTOXIN RESEARCH, 2004, 10 (02) :71-84