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Published on: December 2, 2015
Immunoglobulin production in vitro in major depression: a pilot study on the modulating action of endogenous cortisol
F W Kok1, C J Heijnen, J A Bruijn
1Department of Psychiatry, Academic Hospital, Utrecht, The Netherlands.
Insights
Depressed patients show altered immune responses to hydrocortisone (HCO), with their lymphocytes exhibiting corticosteroid resistance. This suggests differences in how immune cells in depression react to stress hormones compared to healthy individuals.
Area of Science:
- Immunology
- Neuroendocrinology
- Psychiatry
Background:
- Major depression is associated with altered HPA axis activity and immune dysregulation.
- Endogenous cortisol levels may influence immune cell function in depression.
- Hydrocortisone (HCO) is a glucocorticoid with known immunomodulatory effects.
Purpose of the Study:
- To investigate differential sensitivity of immunoglobulin (Ig) production to hydrocortisone (HCO) in depression.
- To examine the relationship between endogenous cortisol levels and immune response to HCO.
- To assess corticosteroid sensitivity of immunocompetent cells in depressed patients.
Main Methods:
- Blood samples collected from 10 depressed patients and 10 healthy controls at 8 AM and 4 PM.
- Peripheral blood lymphocytes cultured with graded concentrations of HCO (10(-9)-10(-5) M).
- Immunoglobulin (IgG and IgM) synthesis assessed with and without pokeweed mitogen (PWM) stimulation.
Main Results:
- Depressed patients had higher mean plasma cortisol levels than controls.
- HCO stimulated IgG and IgM production in controls, with some exceptions.
- HCO stimulated IgG but not IgM in depressed patients without PWM; PWM-driven responses showed differential sensitivity in patients.
Conclusions:
- Differential sensitivity to HCO effects on in vitro IgG and IgM synthesis exists between depressed patients and controls.
- Immunocompetent cells of depressed patients may possess corticosteroid-resistant properties.
- Findings suggest altered glucocorticoid receptor sensitivity or downstream signaling in depression-related immune dysfunction.
Abstract:
To investigate the possible differential sensitivity of hydrocortisone (HCO) on immunoglobulin (Ig) production in depression in relation to endogenous cortisol levels, blood was obtained at 8 AM and 4 PM from 10 inpatients with major depression according to DSM-III-R criteria and 10 age- and sex-matched healthy subjects. Peripheral blood lymphocytes were cultured in the presence of graded concentrations (10(-9)-10(-5) M) of HCO to study the effect on immunoglobulin (IgG and IgM) synthesis. In addition, peripheral blood lymphocytes were cultured in the presence of pokeweed mitogen (PWM) to study any additional effect of graded concentrations of HCO (10(-9)-10(-5) M) on IgG and IgM synthesis. Mean plasma cortisol levels at both time points were higher in patients compared to controls. HCO--preferentially at concentrations of 10(-8)-10(-6) molar--stimulated IgG and IgM production in controls, except for IgM production in the 8 AM samples, when the cells were cultured in the absence of PWM. Under these culture conditions, HCO stimulated IgG but not IgM synthesis in depressed patients. PWM-driven IgG and IgM synthesis in controls was stimulated by HCO in both the 8 AM and the 4 PM samples. In patients PWM driven IgG synthesis was stimulated by HCO in the 8 AM but not in the 4 PM samples. PWM-stimulated IgM synthesis was not augmented by HCO in depressed patients. We conclude that a differential sensitivity to the effects of HCO exists in in vitro IgG and IgM synthesis between depressed patients and controls. Furthermore, we suggest that immunocompetent cells of depressed patients possess corticosteroid-resistant properties.
