Acute Experimental Changes in Mood State Regulate Immune Function in Relation to Central Opioid Neurotransmission: a Model of Human CNS-peripheral Inflammatory Interaction

Overview

Journal Mol Psychiatry

Specialties Molecular Biology
Psychiatry

Date 2015 Aug 19

PMID 26283642

Citations 16

Authors

A R Prossin

A E Koch

P L Campbell

T Barichello

S S Zalcman

J-K Zubieta

Affiliations

Soon will be listed here.

Abstract

Although evidence shows depressed moods enhance risk for somatic diseases, molecular mechanisms underlying enhanced somatic susceptibility are ill-defined. Knowledge of these molecular mechanisms will inform development of treatment and prevention strategies across comorbid depressive and somatic illnesses. Existing evidence suggests that interleukin-18 (IL-18; an IL-1 family cytokine) is elevated in depression and implicated in pathophysiology underlying comorbid medical illnesses. We previously identified strong associations between baseline IL-18 and μ-opioid receptor availability in major depressive disorder (MDD) volunteers. Combined with the evidence in animal models, we hypothesized that experimental mood induction would change IL-18, the extent proportional to opioid neurotransmitter release. Using the Velten technique in a [(11)C]carfentanil positron emission tomography neuroimaging study, we examined the impact of experimentally induced mood (sad, neutral) on plasma IL-18 and relationships with concurrent changes in the central opioid neurotransmission in 28 volunteers (healthy, MDD). Results showed mood induction impacted IL-18 (F2,25=12.2, P<0.001), sadness increasing IL-18 (T27=2.6, P=0.01) and neutral mood reducing IL-18 (T27=-4.1, P<0.001). In depressed volunteers, changes in IL-18 were more pronounced (F2,25=3.6, P=0.03) and linearly proportional to sadness-induced μ-opioid activation (left ventral pallidum, bilateral anterior cingulate cortices, right hypothalamus and bilateral amygdala). These data demonstrate that dynamic changes of a pro-inflammatory IL-1 superfamily cytokine, IL-18, and its relationship to μ-opioid neurotransmission in response to experimentally induced sadness. Further testing is warranted to delineate the role of neuroimmune interactions involving IL-18 in enhancing susceptibility to medical illness (that is, diabetes, heart disease and persistent pain states) in depressed individuals.

Citing Articles

Eight-year total, cognitive-affective, and somatic depressive symptoms trajectories and risks of cardiac events.

Lu X, Liu C, Lu H, Qian X, Wang C, Jia C Transl Psychiatry. 2024; 14(1):356.

PMID: 39231933 PMC: 11374896. DOI: 10.1038/s41398-024-03063-y.

Exploring the role of inflammation in major depressive disorder: beyond the monoamine hypothesis.

Pastis I, Santos M, Paruchuri A Front Behav Neurosci. 2024; 17:1282242.

PMID: 38299049 PMC: 10829100. DOI: 10.3389/fnbeh.2023.1282242.

Serum levels of biomarkers that may link chronic obstructive pulmonary disease and depressive disorder.

Malujlo-Balcerska E, Pietras T, Smigielski W Pharmacol Rep. 2023; 75(6):1619-1626.

PMID: 37921965 PMC: 10661791. DOI: 10.1007/s43440-023-00548-3.

Effects of placebo administration on immune mechanisms and relationships with central endogenous opioid neurotransmission.

Prossin A, Koch A, Campbell P, Laumet G, Stohler C, Dantzer R Mol Psychiatry. 2021; 27(2):831-839.

PMID: 34716408 PMC: 9054677. DOI: 10.1038/s41380-021-01365-x.

Acute acetate administration increases endogenous opioid levels in the human brain: A [C]carfentanil molecular imaging study.

Ashok A, Myers J, Frost G, Turton S, Gunn R, Passchier J J Psychopharmacol. 2021; 35(5):606-610.

PMID: 33406950 PMC: 8155733. DOI: 10.1177/0269881120965912.

References

van de Veerdonk F, Netea M, Dinarello C, Joosten L . Inflammasome activation and IL-1β and IL-18 processing during infection. Trends Immunol. 2011; 32(3):110-6. DOI: 10.1016/j.it.2011.01.003. View

Kennedy S, Koeppe R, Young E, Zubieta J . Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry. 2006; 63(11):1199-208. DOI: 10.1001/archpsyc.63.11.1199. View

Merendino R, Di Rosa A, Di Pasquale G, Minciullo P, Mangraviti C, Costantino A . Interleukin-18 and CD30 serum levels in patients with moderate-severe depression. Mediators Inflamm. 2002; 11(4):265-7. PMC: 1781663. DOI: 10.1080/096293502900000131. View

Velten Jr E . A laboratory task for induction of mood states. Behav Res Ther. 1968; 6(4):473-82. DOI: 10.1016/0005-7967(68)90028-4. View

Nicholson A, Kuper H, Hemingway H . Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J. 2006; 27(23):2763-74. DOI: 10.1093/eurheartj/ehl338. View

Davis M, Whalen P . The amygdala: vigilance and emotion. Mol Psychiatry. 2001; 6(1):13-34. DOI: 10.1038/sj.mp.4000812. View

Puren A, Fantuzzi G, Dinarello C . Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1beta are differentially regulated in human blood mononuclear cells and mouse spleen cells. Proc Natl Acad Sci U S A. 1999; 96(5):2256-61. PMC: 26770. DOI: 10.1073/pnas.96.5.2256. View

Miyoshi K, Obata K, Kondo T, Okamura H, Noguchi K . Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury. J Neurosci. 2008; 28(48):12775-87. PMC: 6671812. DOI: 10.1523/JNEUROSCI.3512-08.2008. View

LAWSON L, Perry V, Gordon S . Turnover of resident microglia in the normal adult mouse brain. Neuroscience. 1992; 48(2):405-15. DOI: 10.1016/0306-4522(92)90500-2. View

10.

Prossin A, Love T, Koeppe R, Zubieta J, Silk K . Dysregulation of regional endogenous opioid function in borderline personality disorder. Am J Psychiatry. 2010; 167(8):925-33. PMC: 6863154. DOI: 10.1176/appi.ajp.2010.09091348. View

11.

Buller K, Crane J, Day T . The central nucleus of the amygdala; a conduit for modulation of HPA axis responses to an immune challenge?. Stress. 2012; 4(4):277-87. DOI: 10.3109/10253890109014752. View

12.

Conti B, PARK L, Calingasan N, Kim Y, Kim H, Bae Y . Cultures of astrocytes and microglia express interleukin 18. Brain Res Mol Brain Res. 1999; 67(1):46-52. DOI: 10.1016/s0169-328x(99)00034-0. View

13.

Ribeiro S, Kennedy S, Smith Y, Stohler C, Zubieta J . Interface of physical and emotional stress regulation through the endogenous opioid system and mu-opioid receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(8):1264-80. DOI: 10.1016/j.pnpbp.2005.08.011. View

14.

Dinarello C . Interleukin-18. Methods. 1999; 19(1):121-32. DOI: 10.1006/meth.1999.0837. View

15.

Bossu P, Salani F, Cacciari C, Picchetto L, Cao M, Bizzoni F . Disease outcome, alexithymia and depression are differently associated with serum IL-18 levels in acute stroke. Curr Neurovasc Res. 2009; 6(3):163-70. DOI: 10.2174/156720209788970036. View

16.

Opstad T, Pettersen A, Arnesen H, Seljeflot I . The co-existence of the IL-18+183 A/G and MMP-9 -1562 C/T polymorphisms is associated with clinical events in coronary artery disease patients. PLoS One. 2013; 8(9):e74498. PMC: 3764212. DOI: 10.1371/journal.pone.0074498. View

17.

Bonnet M, Beloeil H, Benhamou D, Mazoit J, Asehnoune K . The mu opioid receptor mediates morphine-induced tumor necrosis factor and interleukin-6 inhibition in toll-like receptor 2-stimulated monocytes. Anesth Analg. 2008; 106(4):1142-9, table of contents. DOI: 10.1213/ane.0b013e318165de89. View

18.

Zubieta J, Ketter T, Bueller J, Xu Y, Kilbourn M, Young E . Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission. Arch Gen Psychiatry. 2003; 60(11):1145-53. DOI: 10.1001/archpsyc.60.11.1145. View

19.

Sugama S, Kim Y, Baker H, Tinti C, Kim H, Joh T . Tissue-specific expression of rat IL-18 gene and response to adrenocorticotropic hormone treatment. J Immunol. 2000; 165(11):6287-92. DOI: 10.4049/jimmunol.165.11.6287. View

20.

Mallat Z, Corbaz A, Scoazec A, Graber P, Alouani S, Esposito B . Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability. Circ Res. 2001; 89(7):E41-5. DOI: 10.1161/hh1901.098735. View