Enhancing versus suppressive effects of stress hormones on skin immune function - PubMed (original) (raw)

Enhancing versus suppressive effects of stress hormones on skin immune function

F S Dhabhar et al. Proc Natl Acad Sci U S A. 1999.

Abstract

Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoimmunity) aspects of immune function. Contrary to the idea that stress suppresses immunity, we have reported that short-duration stressors significantly enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin may mediate this immunoenhancement. Here, we identify the hormonal mediators of a stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed skin DTH. These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.

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Figures

Figure 1

Figure 1

Adrenalectomy eliminates a stress-induced enhancement of skin DTH. A 6-day time course of changes in thickness of right pinnae of previously sensitized animals challenged with DNFB is shown. Stressed intact (A) and sham (B) animals showed a significant increase in the DTH response compared with unstressed animals. (C) ADX animals did not show a stress-induced increase skin DTH. Data are expressed as means ± SEM (n = 6 per treatment group). Statistically significant differences are indicated. (∗, P < 0.05; ∗∗, P < 0.005, independent t test.)

Figure 2

Figure 2

Acute administration of corticosterone enhances skin DTH. A time course of changes in the thickness of right pinnae of previously sensitized animals challenged with DNFB is shown. Corticosterone (CORT, 5 mg/kg) was administered i.p. to ADX animals (A) or through drinking water (100 or 400 μg/ml) to intact animals (B). Control animals were treated with vehicle: 30% HBC (A) or 0.6% ethanol (B). Corticosterone-treated animals showed a significantly larger DTH response than vehicle-treated animals. (∗, P < 0.05, independent t test.)

Figure 3

Figure 3

Pharmacologic treatment with glucocorticoid hormones suppresses the skin DTH response. A time course of changes in the thickness of right pinnae of previously sensitized animals challenged with DNFB is shown. (A) Corticosterone (CORT, 40 mg/kg) or dexamethasone (DEX, 0.1 mg/kg) was administered acutely. (B) Corticosterone was also administered chronically in drinking water (dw CORT, 400 μg/ml, 6 days). Control animals were treated with vehicle: 30% HBC (A) or 0.6% ethanol (B). Corticosterone- and dexamethasone-treated animals showed lower DTH responses than control animals. (∗, P < 0.05; ∗∗, P < 0.005, independent t test.)

Figure 4

Figure 4

Acute administration of epinephrine enhances skin DTH. A time course of changes in the thickness of right pinnae of previously sensitized animals challenged with DNFB is shown. Epinephrine (EPI, 0.05, 0.25, or 0.5 mg/kg) was administered acutely to ADX animals. Control animals were treated with vehicle (deionized-distilled H2O). Epinephrine-treated animals showed a dose-dependent increase in skin DTH. (∗, P < 0.05; ∗∗, P < 0.005, independent t test.)

Figure 5

Figure 5

Epinephrine and corticosterone additively enhance skin DTH. A time course of changes in the thickness of right pinnae of previously sensitized animals challenged with OXA is shown. Epinephrine (EPI, 0.5 mg/kg), corticosterone (CORT, 5 mg/kg) or epinephrine plus corticosterone (EPI+CORT, 0.5 mg/kg plus 5 mg/kg, respectively) were administered acutely to ADX animals. Control animals were treated with vehicle (VEH, 30% HBC). Epinephrine- or corticosterone-treated animals showed an enhanced DTH response. Moreover, simultaneous administration of the two hormones resulted in an additive enhancement of skin DTH. (∗, P < 0.05; ∗∗, P < 0.005, independent t test.)

Figure 6

Figure 6

Acute administration of stress hormones increases the cellularity of cervical lymph nodes that drain the site of the skin DTH reaction. Epinephrine (EPI, 0.5 mg/kg), corticosterone (CORT, 5 mg/kg), or epinephrine plus corticosterone (EPI+CORT, 0.5 mg/kg plus 5 mg/kg, respectively) were administered to ADX animals. Control animals were treated with vehicle (VEH, 30% HBC). Lymph nodes were collected, and lymphocytes were isolated 48 h after the induction of DTH. Compared with vehicle-treated animals, hormone-treated animals showed higher T lymphocyte numbers in cervical lymph nodes that drain the site of the DTH reaction. (∗, P < 0.05, independent t test.)

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