Summation of behavioral and immunological stress: Metabolic consequences to the growing mouse

To address the hypothesis that multiple stressors can have cumulative effects on the individual, we determined the effects of restraint (R) stress (4 h/day for 7 days), immunological (L) stress [lipopolysac-charide (LPS) injection, 0.45 μg/g body wt on days 6 and 7], and R + L (RL) on the growth and energetics of C57Bl/6 male mice. R and L each repeatedly increased (P < 0.05) circulating corticosterone (>8 times), but RL caused even greater (>250%, P < 0.05) concentrations of circulating corticosterone than did either stressor alone. Only L and RL increased (P < 0.05) circulating interleukin-1β. Although R, L, and RL impaired growth (>75% below controls, P < 0.05), RL reduced growth to a greater extent. All stressors inhibited (P < 0.05) lean (>33% below controls) and fat (>120% below controls) energy deposition, and like the effects on growth, combined RL stress inhibited lean and fat energy deposition to a greater extent than did either stressor acting alone. These results demonstrated that the summation of multiple stress results in a cumulative cost to the growing animal.