Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial
Abstract Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depresse...
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| Format: | Article |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-16364-3 |
| _version_ | 1828329316385030144 |
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| author | Jennifer L. Kruse Chloe C. Boyle Richard Olmstead Elizabeth C. Breen Susannah J. Tye Naomi I. Eisenberger Michael R. Irwin |
| author_facet | Jennifer L. Kruse Chloe C. Boyle Richard Olmstead Elizabeth C. Breen Susannah J. Tye Naomi I. Eisenberger Michael R. Irwin |
| author_sort | Jennifer L. Kruse |
| collection | DOAJ |
| description | Abstract Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression. Given epidemiologic relationships identified between IL-6, tumor necrosis factor (TNF)- α, and subsequent depression, levels of these pro-inflammatory cytokines were also explored as potential moderators of depressed mood response to endotoxin. Secondary analyses were completed on data from healthy adults (n = 114) who completed a double-blind, placebo-controlled randomized trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). IL-8, as well as IL-6 and TNF- α, were measured at baseline prior to infusion, and depressed mood and feelings of social disconnection were assessed approximately hourly. Baseline levels of IL-8, but not IL-6 or TNF-α, moderated depressed mood (β = − 0.274, p = .03) and feelings of social disconnection (β = − 0.307, p = .01) responses, such that higher baseline IL-8 was associated with less increase in depressed mood and feelings of social disconnection in the endotoxin, but not placebo, condition. IL-8 had threshold effects, in which highest quartile IL-8 (≥ 2.7 pg/mL) attenuated increases in depressed mood in response to endotoxin as compared to lower IL-8 quartiles (p = .02). These findings suggest that IL-8 may be a biological factor that mitigates risk of inflammation-associated depression. Clinical trials registration: ClinicalTrials.gov NCT01671150, registration date 23/08/2012. |
| first_indexed | 2024-04-13T20:23:33Z |
| format | Article |
| id | doaj.art-0c4692b1cc37470e8d25f2956c522917 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T20:23:33Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0c4692b1cc37470e8d25f2956c5229172022-12-22T02:31:28ZengNature PortfolioScientific Reports2045-23222022-07-011211910.1038/s41598-022-16364-3Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trialJennifer L. Kruse0Chloe C. Boyle1Richard Olmstead2Elizabeth C. Breen3Susannah J. Tye4Naomi I. Eisenberger5Michael R. Irwin6Norman Cousins Center for PsychoneuroimmunologyNorman Cousins Center for PsychoneuroimmunologyNorman Cousins Center for PsychoneuroimmunologyNorman Cousins Center for PsychoneuroimmunologyQueensland Brain Institute, The University of QueenslandNorman Cousins Center for PsychoneuroimmunologyNorman Cousins Center for PsychoneuroimmunologyAbstract Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression. Given epidemiologic relationships identified between IL-6, tumor necrosis factor (TNF)- α, and subsequent depression, levels of these pro-inflammatory cytokines were also explored as potential moderators of depressed mood response to endotoxin. Secondary analyses were completed on data from healthy adults (n = 114) who completed a double-blind, placebo-controlled randomized trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). IL-8, as well as IL-6 and TNF- α, were measured at baseline prior to infusion, and depressed mood and feelings of social disconnection were assessed approximately hourly. Baseline levels of IL-8, but not IL-6 or TNF-α, moderated depressed mood (β = − 0.274, p = .03) and feelings of social disconnection (β = − 0.307, p = .01) responses, such that higher baseline IL-8 was associated with less increase in depressed mood and feelings of social disconnection in the endotoxin, but not placebo, condition. IL-8 had threshold effects, in which highest quartile IL-8 (≥ 2.7 pg/mL) attenuated increases in depressed mood in response to endotoxin as compared to lower IL-8 quartiles (p = .02). These findings suggest that IL-8 may be a biological factor that mitigates risk of inflammation-associated depression. Clinical trials registration: ClinicalTrials.gov NCT01671150, registration date 23/08/2012.https://doi.org/10.1038/s41598-022-16364-3 |
| spellingShingle | Jennifer L. Kruse Chloe C. Boyle Richard Olmstead Elizabeth C. Breen Susannah J. Tye Naomi I. Eisenberger Michael R. Irwin Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial Scientific Reports |
| title | Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial |
| title_full | Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial |
| title_fullStr | Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial |
| title_full_unstemmed | Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial |
| title_short | Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial |
| title_sort | interleukin 8 and depressive responses to an inflammatory challenge secondary analysis of a randomized controlled trial |
| url | https://doi.org/10.1038/s41598-022-16364-3 |
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