title: Restraint stress fails to modulate cutaneous hypersensitivity responses in mice lacking the adenosine A1 receptor.
abstract: Psychological stress has long been associated with effects on immune function and disease. In particular, differential effects of acute and chronic stress on skin immunity occur in the rodent restraint stress model, with acute stress enhancing and chronic stress suppressing cutaneous hypersensitivity. Extracellular levels of adenosine are known to modulate diverse biological activities in the CNS and peripheral tissues and serve an important protective function against physiological stressors such as inflammation and ischemia. In this study, we utilized the restraint stress model and the skin sensitizer dinitrofluorobezene to test the hypothesis that perceived stress influences contact hypersensitivity through an adenosine A(1) receptor-mediated mechanism. We subjected hapten-sensitized A(1) receptor knockout (A1 KO) mice and their wild-type (WT) littermates to either acute (2.5 h) or chronic (5 h daily × 4 weeks) restraint stress, followed by hapten re-challenge of the pinna. Daily measurements of the resulting pinna swellings from each group were compared to reactions in non-stressed controls. In WT mice, pinna swelling was augmented in acutely stressed mice and suppressed in the chronically stressed group. In contrast, contact hypersensitivity responses in the A1 KO mice failed to be affected by either acute or chronic stress. Absence of the adenosine A(1) receptor did not affect levels of plasma corticosterone or urine catecholamines under these stressful conditions but did lead to reduced numbers of circulating neutrophil granulocytes compared to stressed WT animals. These results suggest that the adenosine A(1) receptor pathway plays a role in the process by which perceived psychological stress influences the contact hypersensitivity response.
authors.affiliation: Department of Medicine, New York University School of Medicine, NBV16N-1, 550 First Avenue, New York, NY, 10016, USA, stephen.oliver@nyumc.org.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Oliver
authors.forename: Sneha
authors.initials: S
authors.lastname: Mathew
authors.forename: Tuère F
authors.initials: TF
authors.lastname: Wilder
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Cronstein