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Social stress induces glucocorticoid resistance in macrophages
J L Stark1, R Avitsur, D A Padgett
1Neuroscience Graduate Studies Program, The Ohio State University Health Sciences Center, Columbus, Ohio 43218, USA.
Abstract:
Stress-induced levels of plasma glucocorticoid hormones are known to modulate leukocyte function. These experiments examined the effects of a social stressor on the responsiveness of peripheral immune cells. Male mice experienced six evening cycles of social disruption (SDR), in which an aggressive male intruder was placed into their home cage for 2 h. Although circulating corticosterone was elevated in SDR mice, they had enlarged spleens and increased numbers of splenic leukocytes. Splenocytes from SDR and control mice were cultured with lipopolysaccharide and corticosterone. Cells from SDR mice exhibited decreased sensitivity to the antiproliferative effects of corticosterone, suggesting that the peripheral immune cells were resistant to glucocorticoids. In addition, SDR cells produced more interleukin (IL)-6. To determine which cell population was affected, we used antibody-labeled magnetic beads to deplete splenocyte suspensions of B cells or macrophages. Depletion of macrophages from SDR cultures, but not depletion of B cells, abolished both the corticosterone resistance and enhanced IL-6 secretion. These findings demonstrate that a psychosocial stressor induced glucocorticoid resistance in mouse splenic macrophages.
Insights
Social disruption stress in mice led to enlarged spleens and immune cells resistant to glucocorticoids. Macrophages, not B cells, were responsible for this stress-induced glucocorticoid resistance and increased IL-6 production.
Area of Science:
- Immunology
- Neuroscience
- Endocrinology
Background:
- Glucocorticoid hormones, like corticosterone, are known to regulate leukocyte function.
- Psychosocial stress can significantly alter immune cell activity and hormone levels.
Purpose of the Study:
- To investigate the impact of social disruption stress on the responsiveness of peripheral immune cells to glucocorticoids.
- To identify specific immune cell populations mediating stress-induced changes in immune function.
Main Methods:
- Male mice were subjected to repeated social disruption stress (SDR).
- Circulating corticosterone levels, spleen size, and splenic leukocyte numbers were measured.
- Splenocytes were cultured with lipopolysaccharide and corticosterone to assess glucocorticoid sensitivity and IL-6 production.
- Macrophages and B cells were depleted using magnetic beads to identify key cell populations.
Main Results:
- SDR mice exhibited elevated corticosterone but also enlarged spleens and increased splenic leukocytes.
- Splenocytes from SDR mice showed reduced sensitivity to the antiproliferative effects of corticosterone (glucocorticoid resistance).
- SDR splenocytes produced higher levels of interleukin-6 (IL-6).
- Depletion of macrophages, but not B cells, from SDR cultures reversed glucocorticoid resistance and normalized IL-6 secretion.
Conclusions:
- Psychosocial stress induces glucocorticoid resistance in mouse splenic macrophages.
- Macrophages play a critical role in mediating stress-induced alterations in immune cell glucocorticoid sensitivity and inflammatory cytokine production.