Chronic Psychologic Stress in Mice Induces Kidney Inflammation

Chronic stress elevates neutrophil gelatinase-associated lipocalin and cystatin C. Chronic stress increases T helper 17 and regulatory T-cell populations in the kidney. Chronic stress could increase susceptibility to kidney diseases.

Chronic stress (CS) due to prolonged exposure to negative life events increases the risk of psychiatric illnesses and significantly affects physiologic processes. CS has also been linked to sustained systemic inflammation, resulting in dysregulated immune responses and organ function. We hypothesized that CS would lead to kidney inflammation and tested this in mice.

Male C57BL/6J mice were subjected to CS by pair-housing them with CD-1 retired breeder mice. Kidney immune cells were isolated and evaluated by spectral flow cytometry. Cytokines were measured using a multiplex assay in kidney tissue and serum. Serum creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin levels were measured.

Mice subjected to CS exhibited greater weight gain than the control group and had reduced fur quality. CS led to a decrease in the percentage of kidney CD4 + T cells (54.26%±0.89% versus 59.88%±1.25%, P < 0.001) and an increase in T helper 17 (2.3%±0.3% versus 0.83%±0.15%, P < 0.001) and regulatory T cells (3.42%±0.45% versus 1.53%±0.21%, P < 0.001). There was an increase in the kidney macrophage percentage in CS mice (88.33%±1.16% versus 84.26%±0.73%, P < 0.01). TNF- α levels were higher in the kidney of stressed mice (8.53±1.18 versus 3.15±1.29 pg/ml, P < 0.01). CS led to elevated levels of serum cystatin C (515.9±16.88 versus 456.6±14.79 ng/ml, P < 0.05) serum neutrophil gelatinase-associated lipocalin (833.1±282.4 versus 90.58±5.57 ng/ml, P < 0.0001).

CS in mice led to kidney inflammation and immunologic changes. These could predispose to acute and CKDs in which inflammation plays a pathogenic role.