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PMID: 16677721 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Feeding, exploratory, anxiety- and depression-related behaviors are not altered in interleukin-6-deficient male mice.

Behavioural brain research ·Vol. 171 ·No. 1 ·2006-07-15 ·Pages 94-108

Swiergiel AH, Dunn AJ

Abstract

Interleukin-6 (IL-6) has been implicated in behavioral responses associated with inflammation, sickness behavior and various nervous system disorders. We studied a range of different behaviors in IL-6-knockout (IL-6ko) and wild-type (WT) male mice. No significant differences were observed in ambulatory, exploratory, and stereotypic activities in home or novel cages, in an open field (OF), in the multicompartment chamber (MCC), or in the elevated plus-maze (EPM). IL-6ko mice shed fewer fecal boli than WT mice in the OF, in novel cages and in the MCC although this effect was not statistically significant in the OF. In novel cages, intraperitoneal (i.p.) injection of IL-6 (1 microg) depressed ambulatory activity slightly more in IL-6ko than in WT mice. Restraint and interleukin-1beta (IL-1beta, 100 ng i.p.) decreased exploration of mice in the MCC and EPM, but there was no indication of altered sensitivity in IL-6ko mice. No significant differences were detected in the tail suspension and the Porsolt forced swim tests. IL-1beta and lipopolysaccharide (LPS 1 microg i.p.) injection depressed sweetened milk and solid food intake similarly in IL-6ko and WT mice, but IL-6 had no effect, suggesting that IL-6 is not involved in these effects of IL-1 or LPS. However, IL-1beta and LPS depressed body weight more in WT than in IL-6ko mice. Plasma corticosterone and basal concentrations of catecholamines, indoleamines and their metabolites in several brain regions were similar. The responses in these measures to IL-1beta and LPS were also similar, except that there were no significant changes in tryptophan and serotonin metabolism in IL-6ko mice. This may reflect a role for IL-6 in the tryptophan and serotonin responses to IL-1 and LPS. It is concluded that the lack of IL-6 is not associated with substantial alterations in several different mouse behaviors, and in the responses to restraint, IL-1beta, IL-6 and LPS.

MeSH Terms
Adrenocorticotropic Hormone/blood Analysis of Variance Animals Anxiety/blood,immunology Biogenic Amines/metabolism Brain/immunology,metabolism Corticosterone/blood Depression/blood,immunology Eating/immunology Exploratory Behavior/physiology Feeding Behavior/physiology Interleukin-1/physiology Interleukin-6/genetics,immunology Lipopolysaccharides/immunology Male Mice Mice, Inbred BALB C Mice, Knockout Motor Activity/immunology Restraint, Physical Sick Role Stress, Psychological/immunology,metabolism
Chemicals
Biogenic Amines Interleukin-1 Interleukin-6 Lipopolysaccharides Adrenocorticotropic Hormone Corticosterone
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Swiergiel Artur H
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, 71130-3932, USA. aswier@lsuhsc.edu
Dunn Adrian J
References (83)
83 references, click to expand
  1. Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications.
    J Clin Endocrinol Metab. 2005 May;90(5):2522-30 PMID: 15705924
  2. Role of interleukin-6 in mortality from and physiologic response to sepsis.
    Infect Immun. 2005 May;73(5):2751-7 PMID: 15845478
  3. Experimental cancer cachexia: the role of host-derived cytokines interleukin (IL)-6, IL-12, interferon-gamma, and tumor necrosis factor alpha evaluated in gene knockout, tumor-bearing mice on C57 Bl background and eicosanoid-dependent cachexia.
    Cancer Res. 2000 Oct 1;60(19):5488-93 PMID: 11034092
  4. Impaired immune and acute-phase responses in interleukin-6-deficient mice.
    Nature. 1994 Mar 24;368(6469):339-42 PMID: 8127368
  5. QTL analysis of multiple behavioral measures of anxiety in mice.
    Behav Genet. 2004 May;34(3):267-93 PMID: 14990867
  6. Selection for body weight induces differences in exploratory behavior and learning in mice.
    Acta Neurobiol Exp (Wars). 2005;65(3):243-53 PMID: 16130798
  7. The role of interleukin-6 in the activation of the hypothalamo-pituitary-adrenocortical axis and brain indoleamines by endotoxin and interleukin-1 beta.
    Brain Res. 1999 Jan 9;815(2):337-48 PMID: 9878816
  8. Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection.
    Viral Immunol. 2005;18(1):41-78 PMID: 15802953
  9. Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice.
    Pharmacol Biochem Behav. 2005 Jul;81(3):688-93 PMID: 15982728
  10. Discriminant power of combined cerebrospinal fluid tau protein and of the soluble interleukin-6 receptor complex in the diagnosis of Alzheimer's disease.
    Brain Res. 1999 Mar 27;823(1-2):104-12 PMID: 10095017
  11. Beta-adrenergic receptors are involved in stress-related behavioral changes.
    Pharmacol Biochem Behav. 1993 May;45(1):1-7 PMID: 8100069
  12. Cytokines as mediators of depression: what can we learn from animal studies?
    Neurosci Biobehav Rev. 2005;29(4-5):891-909 PMID: 15885777
  13. Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers.
    J Psychiatr Res. 1995 Mar-Apr;29(2):141-52 PMID: 7666381
  14. Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis.
    Am J Physiol. 1997 Feb;272(2 Pt 2):R621-30 PMID: 9124487
  15. Reduced exercise endurance in interleukin-6-deficient mice.
    Endocrinology. 2004 Jun;145(6):2680-6 PMID: 14988384
  16. The concept of sickness behavior: a brief chronological account of four key discoveries.
    Vet Immunol Immunopathol. 2002 Sep 10;87(3-4):443-50 PMID: 12072271
  17. Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement.
    Arthritis Rheum. 1990 May;33(5):644-9 PMID: 2346520
  18. Plasma and cerebrospinal fluid interleukin-6 concentrations in posttraumatic stress disorder.
    Neuroimmunomodulation. 2001;9(4):209-17 PMID: 11847483
  19. [Physiology of fecal continence and defecation].
    Arch Int Physiol Biochim Biophys. 1991 Sep;99(5):A53-63 PMID: 1720692
  20. Role of interleukin-6 and transforming growth factor-beta in anorexia nervosa.
    Biol Psychiatry. 1994 Dec 15;36(12):836-9 PMID: 7893847
  21. Glucocorticoids alter fever and IL-6 responses to psychological stress and to lipopolysaccharide.
    Am J Physiol. 1993 May;264(5 Pt 2):R1010-6 PMID: 8498588
  22. Behavioural characterization of interleukin-6 overexpressing or deficient mice during agonistic encounters.
    Eur J Neurosci. 1998 Dec;10(12):3664-72 PMID: 9875345
  23. Characterization of early cytokine responses and an interleukin (IL)-6-dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection.
    J Exp Med. 1997 Apr 7;185(7):1185-92 PMID: 9104805
  24. Endotoxin, tumor necrosis factor-alpha and interleukin 1 induce interleukin 6 production in vivo.
    Clin Immunol Immunopathol. 1989 Dec;53(3):488-98 PMID: 2805453
  25. Limitations on the use of the C57BL/6 mouse in the tail suspension test.
    Psychopharmacology (Berl). 2001 Apr;155(1):110-2 PMID: 11374330
  26. Peripheral interleukin-6 administration increases extracellular concentrations of serotonin and the evoked release of serotonin in the rat striatum.
    Neurochem Int. 2001 Apr;38(4):303-8 PMID: 11137624
  27. Cognitive function in young and adult IL (interleukin)-6 deficient mice.
    Behav Brain Res. 2004 Aug 31;153(2):423-9 PMID: 15265638
  28. Diurnal variation of lipopolysaccharide-induced alterations in sleep and body temperature of interleukin-6-deficient mice.
    Brain Behav Immun. 2005 Jan;19(1):40-51 PMID: 15581737
  29. The role of cytokines in the behavioral responses to endotoxin and influenza virus infection in mice: effects of acute and chronic administration of the interleukin-1-receptor antagonist (IL-1ra).
    Brain Res. 1997 Nov 21;776(1-2):96-104 PMID: 9439800
  30. Interleukin-6: an overview.
    Annu Rev Immunol. 1990;8:253-78 PMID: 2188664
  31. Physiological and pathological roles of interleukin-6 in the central nervous system.
    Mol Neurobiol. 1997 Dec;15(3):307-39 PMID: 9457704
  32. Interleukin-6: from basic science to medicine--40 years in immunology.
    Annu Rev Immunol. 2005;23:1-21 PMID: 15771564
  33. Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice.
    Physiol Behav. 2000 Aug-Sep;70(3-4):367-73 PMID: 11006436
  34. Mouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and serotonin metabolism.
    Neurochem Int. 1998 Aug;33(2):143-54 PMID: 9761458
  35. Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats.
    Biochem Biophys Res Commun. 1988 Sep 30;155(3):1459-63 PMID: 2845968
  36. The tail suspension test: a new method for screening antidepressants in mice.
    Psychopharmacology (Berl). 1985;85(3):367-70 PMID: 3923523
  37. Biology of interleukin 1.
    FASEB J. 1988 Feb;2(2):108-15 PMID: 3277884
  38. Interleukin-2 and -6 induce behavioral-activating effects in mice.
    Brain Res. 1998 Nov 16;811(1-2):111-21 PMID: 9804916
  39. Endocrinologic and metabolic effects of interleukin-6 in humans.
    Am J Physiol. 1995 May;268(5 Pt 1):E813-9 PMID: 7762632
  40. Tumor necrosis factor alpha and interleukin-6 have differential effects on food intake and gastric emptying in fasted rats.
    Res Nurs Health. 2000 Jun;23(3):222-8 PMID: 10871537
  41. Role of cytokines in cancer cachexia in a murine model of intracerebral injection of human tumours.
    Cytokine. 2001 Jul 7;15(1):27-38 PMID: 11509006
  42. Systemic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone.
    Life Sci. 1988;43(5):429-35 PMID: 3260987
  43. Chronic mild stress in mice decreases peripheral cytokine and increases central cytokine expression independently of IL-10 regulation of the cytokine network.
    Neuroimmunomodulation. 2002-2003;10(6):359-66 PMID: 12907843
  44. Interleukin-6 (IL-6)--a molecule with both beneficial and destructive potentials.
    Prog Neurobiol. 1997 Aug;52(5):379-90 PMID: 9304698
  45. Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain.
    Eur J Neurosci. 1993 Nov 1;5(11):1426-35 PMID: 8287192
  46. Interleukin-6 in cerebrospinal fluid of patients with central nervous system infections.
    Acta Paediatr. 1995 Aug;84(8):879-83 PMID: 7488810
  47. Behavioral effects of cytokines.
    Brain Behav Immun. 2001 Dec;15(4):371-87 PMID: 11782104
  48. Dietary ethyl-eicosapentaenoic acid but not soybean oil reverses central interleukin-1-induced changes in behavior, corticosterone and immune response in rats.
    Stress. 2004 Mar;7(1):43-54 PMID: 15204032
  49. Behavioral effects of infection with IL-6 adenovector.
    Brain Behav Immun. 2001 Mar;15(1):25-42 PMID: 11259078
  50. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes.
    FEBS Lett. 1989 Jan 2;242(2):237-9 PMID: 2464504
  51. Interleukin-1 induces changes in norepinephrine metabolism in the rat brain.
    Brain Behav Immun. 1988 Sep;2(3):267-74 PMID: 3266560
  52. Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice.
    Infect Immun. 1997 Jun;65(6):2339-45 PMID: 9169772
  53. Temporal cascade of plasma level surges in ACTH, corticosterone, and cytokines in endotoxin-challenged rats.
    Am J Physiol. 1994 Jul;267(1 Pt 2):R164-70 PMID: 8048620
  54. Mapping quantitative trait loci for anxiety in chromosome substitution strains of mice.
    Genetics. 2005 Feb;169(2):855-62 PMID: 15371360
  55. Muscle-derived interleukin-6--a possible link between skeletal muscle, adipose tissue, liver, and brain.
    Brain Behav Immun. 2005 Sep;19(5):371-6 PMID: 15935612
  56. Soluble interleukin-6 (IL-6) receptor augments central effects of IL-6 in vivo.
    FASEB J. 1995 May;9(8):659-64 PMID: 7768358
  57. Immobilization stress may increase plasma interleukin-6 via central and peripheral catecholamines.
    Neuroimmunomodulation. 1994 Nov-Dec;1(6):335-42 PMID: 7671121
  58. Behavioral despair in mice: a primary screening test for antidepressants.
    Arch Int Pharmacodyn Ther. 1977 Oct;229(2):327-36 PMID: 596982
  59. Central administration of rat IL-6 induces HPA activation and fever but not sickness behavior in rats.
    Am J Physiol. 1999 Mar;276(3):R652-8 PMID: 10070124
  60. The roles of IL-1, IL-6, and TNFalpha in the feeding responses to endotoxin and influenza virus infection in mice.
    Brain Behav Immun. 1999 Sep;13(3):252-65 PMID: 10469526
  61. The acute phase response.
    Immunol Today. 1994 Feb;15(2):74-80 PMID: 7512342
  62. Endotoxin tolerance: a review.
    Crit Care Med. 2002 Jan;30(1 Suppl):S64-73 PMID: 11782563
  63. Differential effects of interleukin (IL)-1beta, IL-2 and IL-6 on responding for rewarding lateral hypothalamic stimulation.
    Brain Res. 1998 Jan 1;779(1-2):177-87 PMID: 9473665
  64. Corticotropin-releasing factor elicits naloxone sensitive stress-like alterations in exploratory behavior in mice.
    Regul Pept. 1986 Dec 1;16(1):83-93 PMID: 3492730
  65. Interleukin-6 in biology and medicine.
    Adv Immunol. 1993;54:1-78 PMID: 8379461
  66. Amyotrophic lateral sclerosis: interleukin-6 levels in cerebrospinal fluid.
    Can J Neurol Sci. 1992 Aug;19(3):357-9 PMID: 1393846
  67. Stress-related changes in cerebral catecholamine and indoleamine metabolism: lack of effect of adrenalectomy and corticosterone.
    J Neurochem. 1988 Aug;51(2):406-12 PMID: 2455773
  68. Cerebrospinal cytokine levels in patients with acute depression.
    Neuropsychobiology. 1999 Nov;40(4):171-6 PMID: 10559698
  69. Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparison with interleukin-1.
    J Pharmacol Exp Ther. 1992 Jun;261(3):964-9 PMID: 1602402
  70. Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha on the core body temperature of mice.
    Neuroimmunomodulation. 1997 Sep-Dec;4(5-6):230-6 PMID: 9650815
  71. Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6.
    Brain Res. 1994 Apr 18;643(1-2):40-9 PMID: 7518332
  72. Cerebrospinal fluid interleukin (IL)-6 in unipolar major depression.
    J Affect Disord. 2004 Apr;79(1-3):285-9 PMID: 15023509
  73. Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes.
    Brain Res. 1996 Mar 25;713(1-2):143-52 PMID: 8724985
  74. The biological effects of interleukin 6.
    Med Res Rev. 1996 Jan;16(1):87-109 PMID: 8788215
  75. Effects of dietary n-3 or n-6 fatty acids on interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats.
    J Lipid Res. 2003 Oct;44(10):1984-91 PMID: 12837849
  76. Reduced preference for sucrose in autoimmune mice: a possible role of interleukin-6.
    Brain Res Bull. 1997;44(2):155-65 PMID: 9292205
  77. Interleukin-6 and the soluble IL-6 receptor are decreased in cerebrospinal fluid of geriatric patients with major depression: no alteration of soluble gp130.
    Neurosci Lett. 1999 Jan 15;259(3):145-8 PMID: 10025579
  78. The role of interleukin-6 in stress-induced hyperthermia and emotional behaviour in mice.
    Behav Brain Res. 2003 Sep 15;144(1-2):49-56 PMID: 12946594
  79. Influenza virus infection of mice induces anorexia: comparison with endotoxin and interleukin-1 and the effects of indomethacin.
    Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):389-96 PMID: 9164599
  80. In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice.
    Mol Psychiatry. 2004 Apr;9(4):326-57 PMID: 14743184
  81. Induction of interleukin 6 by human and murine recombinant interleukin 1 in mice.
    Eur J Immunol. 1990 Mar;20(3):691-4 PMID: 2318254
  82. Sleep-wake behavior and responses of interleukin-6-deficient mice to sleep deprivation.
    Brain Behav Immun. 2005 Jan;19(1):28-39 PMID: 15581736
  83. The relationship of depression and stressors to immunological assays: a meta-analytic review.
    Brain Behav Immun. 2001 Sep;15(3):199-226 PMID: 11566046
Article Info
Journal
Behavioural brain research
Abbr.
Behav Brain Res
ISSN
0166-4328
Published
2006-07-15
Epub
2006-00-03
Pages
94-108
Language
English
Region
Netherlands
NLM ID
8004872
PMCID
PMC1975690
Subset
IM
Grants
NINDS NIH HHS · R01 NS035370 · United States
NINDS NIH HHS · R01 NS035370-10 · United States
NINDS NIH HHS · R01 NS035370-11 · United States
NINDS NIH HHS · NS35370 · United States
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