Elevated Serum IL-2 Levels are Associated With Major Depressive Disorder: A Case-Control Study

Abstract

Objectives: Numerous earlier studies have stated an association between major depressive disorder (MDD) and altered expression of inflammatory process. However, it still needs to determine whether the alteration of cytokines is the causative factor or a consequence of this disorder. Therefore, we attempted to evaluate the role of the pro-inflammatory cytokine IL-2 in the pathophysiology of depression. Methods: We collected blood samples from 111 MDD patients and 112 healthy controls (HCs) matched by age and sex. Diagnostic and statistical manual of mental disorders (DSM-5) score was used to assess study participants. We determined the severity of depression using the Hamilton Depression (Ham-D) rating scale. We assayed serum levels of IL-2 using the Enzyme-Linked Immunosorbent Assay (ELISA) kit. Results: Elevated levels of IL-2 were detected in MDD patients than HCs (29.79 ± 6.18 and 12.77 ± 4.84 pg/ml, P < 0.05). We observed a higher level of IL-2 in female MDD patients compared to female HCs (31.98 ± 8.34 and 7.76 ± 0.36 pg/ml, P < 0.05). We witnessed a sex-specific correlation between the serum IL-2 levels and the Ham-D score and found that the females with higher Ham-D scores had higher serum IL-2 levels. Moreover, the ROC curve represented the good diagnostic performance of serum IL-2 levels as a biomarker with sensitivity and specificity values of 83.7% and 80.4%, respectively. Conclusions: The current study findings indicate that elevated serum IL-2 levels are associated with MDD. This alteration may be the cause of triggering depression or a result of the activated inflammatory process during the depression. Therefore, we recommend further interventional research to clarify the actual reasons for these altered IL-2 levels in MDD patients.

Elevated Serum Macrophage Migration Inhibitory Factor Levels are Associated With Major Depressive Disorder

“…Elevated inflammatory variables are related to insufficient response to antidepressants which can be possible diagnostic and therapeutic targets for MDD. 59 - 64 Anti-inflammatory agents or immunomodulators can be prescribed as monotherapy or with antidepressants to combat MDD, as stated by authors after conducting a randomized clinical trial. These clinically evaluated anti-inflammatory drugs, including minocycline, statins, pioglitazone, and glucocorticoids, cytokine inhibitors, were observed to have a counter-effect on depressive symptoms.…”

Evaluation of serum MIP-1β and MCP-2 levels in major depressive disorder: A case-control study

“…This poses a substantial public health challenge with wide-ranging consequences [6][7][8]. MDD imposes a significant burden, impacting the affected individuals and their communities, families, and healthcare systems [9][10][11][12]. A complex interplay of biological, neuroendocrine, neuroinflammatory, and structural alterations within the brain comprise the pathophysiology of MDD [13][14][15].…”

Association of interleukin-2 and interleukin-10 with the pathophysiology and development of generalized anxiety disorder: a case-control study

“…IL-2 has been shown to impair synaptic plasticity and cause neuroinflammation, which ultimately leads to neuronal damage in neurocircuits associated with fear and anxiety signal transduction. IL-2 was also reported to act as a potent modulator of NMDA and kainite-mediated excitability in mesolimbic or mesostriatal systems [36][37][38] and thus affect neuroplasticity. As IL-2 was found to be positively associated with major depressive disorder [38,39], probably, IL-2 might also be correlated with anxiety disorders like GAD, as MDD and GAD are highly co-morbid themselves and thus might share common pathophysiological factors.…”

“…IL-2 was also reported to act as a potent modulator of NMDA and kainite-mediated excitability in mesolimbic or mesostriatal systems [36][37][38] and thus affect neuroplasticity. As IL-2 was found to be positively associated with major depressive disorder [38,39], probably, IL-2 might also be correlated with anxiety disorders like GAD, as MDD and GAD are highly co-morbid themselves and thus might share common pathophysiological factors. Recently, a preclinical study conducted by Gilio et al, (2022) observed that IL-2 administration in experimentally healthy mice triggered marked anxiety and depression-like behaviors, and the authors suggested that inhibition of GABA-mediated synaptic inhibitory neurotransmission was involved in the pathology of anxiety [40].…”