Relationship between inflammatory cytokines related with Th17 immunoregulatory and depression severity in patients with depression / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To explore the relationship between Th17 immunoregulatory system and depression and reveal the mechanism of depression from the perspective of neuroimmunity, as well to look for biomarkers that can be used to diagnose, evaluate and predict recurrence of depression.Methods:A total of 91 patients with depression including 45 first-episode patients (FED group) and 46 recurrent episodes patients (RMDD group) were collected who were admitted to Psychiatry Department of the First Affiliated Hospital of Zhengzhou University from March 2019 to May 2020. And 40 healthy controls matched with depression patients in age, gender and education level were collected as control group (HC group). The levels of eight inflammatory cytokines in Th17 immunoregulatory system (five pro-inflammatory cytokines IL-1β, IL-6, IL-17A, IL-21, IL-23; three anti-inflammatory cytokines TGF-β1, IL-10, and IL-27) were measured by enzyme-linked immunosorbent assay (ELISA). Hamilton depression scale-24 (HAMD-24) was used to evaluate the severity of depressive symptoms. Data analyses were performed with SPSS 23.0.Two independent samples t-test, one-way ANOVA, Mann Whitney U test and Kruskal Wallis H test were used for comparison between groups. Results:(1) Comparison of FED group, RMDD group and HC group showed that the levels of pro-inflammatory cytokines IL-1β (5.321(1.317, 21.287)ng/L, 11.277(4.315, 26.167) ng/L, 8.126(1.179, 9.287) ng/L), IL-6(7.787(2.077, 16.778) ng/L, 5.290(2.364.14.475) ng/L, 4.389(1.453, 4.491) ng/L), IL-21 (6.777(6.293, 9.198) ng/L, 7.261(6.293, 25.058)ng/L, 5.097(3.033, 6.507) ng/L) and anti-inflammatory cytokines TGF-β1 (59.098(13.491, 125.368) ng/L, 46.230(18.852, 122.559) ng/L, 25.292(2.716, 31.874) ng/L), IL-10 (226.930(105.117, 449.444) ng/L, 193.929(109.014, 468.269) ng/L, 131.429(77.587, 157.497) ng/L) and IL-27 (0.968(0.651, 1.879)ng/L, 1.859(0.690, 6.221) ng/L, 0.865(0.679, 1.287)ng/L) in plasma were statistically different( H=7.219, 9.482, 18.989, 16.166, 11.511, 6.262, all P<0.05), while the levels of pro-inflammatory cytokines IL-17A (2.175(1.031, 7.975)ng/L, 3.576(1.896, 11.611)ng/L, 3.807(1.301, 4.710)ng/L)and IL-23 (15.708(2.898, 114.175) ng/L, 26.893(9.282, 58.592) ng/L, 17.041(5.027, 23.613)ng/L) were not statistically significant ( H=2.179, 4.305, both P>0.05). Further pairwise comparisons showed that the levels of pro-inflammatory cytokines IL-6, IL-21 and anti-inflammatory cytokines TGF-β1 and IL-10 in plasma of FED group were higher than those of HC group, and the differences were statistically significant (all P<0.05). The levels of pro-inflammatory cytokines IL-1β, IL-6, IL-21 and anti-inflammatory cytokines TGF-β1, IL-10, IL-27 in RMDD group were higher than those in HC group, and the differences were statistically significant (all P<0.05). There were no significant differences in the eight inflammatory cytokines between FED group and RMDD group (all P>0.05). (2) Spearman correlation analysis showed that IL-1β was positively correlated with total score of HAMD-24 ( r=0.286, P<0.05). IL-6 was positively correlated with total score of HAMD-24 and factor score of anxiety or somatization ( r=0.390, 0.291, both P<0.05). TGF-β1 was negatively correlated with total score of HAMD-24 and factor scores of anxiety or somatization and cognitive impairment ( r=-4.200, -0.321, - 0.361, all P<0.05). IL-21 was positively correlated with factor score of sleep ( r=0.319, P<0.05); IL-10 was negatively correlated with total score of HAMD-24 and factor score of cognitive impairment ( r=-0.306, - 0.270, both P<0.05). There was no significant correlation between other inflammatory cytokines and total score of HAMD-24 and seven factor scores (all P>0.05). Conclusion:There is an imbalance in pro-and anti-inflammatory cytokines of Th17 immunoregulatory system in patients with depression, which is more obvious in recurrent episodes patients.The level of immune activation of Th17 immunoregulatory system may be associated with the severity of clinical symptoms, in which the inflammatory cytokine IL-6 may be a biomarker of major depressive disorder; TGF-β1 and IL-21 may be associated with depressive cognitive impairment and sleep.