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Effect of stress on interleukin-2 receptor expression by bovine mononuclear leukocytes
H C Lan1, P G Reddy, M A Chambers
1Department of Microbiology and Pathology, Tuskegee University, AL 36088, USA.
Insights
Dexamethasone (DEX) treatment in calves suppressed immune responses by reducing interleukin-2 receptor (IL-2R) alpha expression. Stress-induced immunosuppression in calves may involve decreased IL-2R alpha and IL-12.
Area of Science:
- Veterinary Immunology
- Immunopharmacology
- Animal Science
Background:
- Corticosteroids like dexamethasone (DEX) are potent immunosuppressants.
- Understanding their effects on young animals is crucial for health management.
- Interleukin-2 receptor (IL-2R) alpha is vital for T-cell activation.
Purpose of the Study:
- To investigate the impact of dexamethasone (DEX) on immune cell function in Holstein calves.
- To explore the role of Interleukin-2 receptor (IL-2R) alpha expression in DEX-induced immunosuppression.
- To assess the potential involvement of IL-2R alpha and IL-12 in stress-induced immune changes in calves.
Main Methods:
- Holstein calves received intramuscular injections of dexamethasone (DEX).
- Peripheral blood mononuclear cells (PBMC) were analyzed for IL-2R alpha expression via flow cytometry.
- PBMC proliferation assays were conducted using T-cell mitogens (PHA, Con A) with and without recombinant human IL-12 (rhu IL-12).
- Calf transport stress was simulated to evaluate its effects on IL-2R alpha expression.
Main Results:
- DEX treatment induced transient lymphopenia and neutrophilia.
- DEX significantly decreased IL-2R alpha expression on Concanavalin A (Con A)-activated PBMC on Days 1 and 2 post-injection.
- Reduced IL-2R alpha expression correlated with diminished PBMC proliferative responses to PHA and Con A.
- Recombinant human IL-12 (rhu IL-12) enhanced proliferative responses, with a greater effect observed in DEX-treated calves.
- Transport stress also led to reduced IL-2R alpha expression in PBMC.
- A trend toward higher creatine kinase (CK) levels was noted in DEX-treated calves.
Conclusions:
- Dexamethasone (DEX) suppresses key immune cell functions in calves, including IL-2R alpha expression and mitogen responsiveness.
- Stress-induced immunosuppression in calves appears to involve decreased IL-2R alpha expression and potentially reduced IL-12 production.
- These findings highlight the impact of corticosteroids and stress on calf immunity, suggesting mechanisms involving IL-2R alpha and IL-12 pathways.
Abstract:
Holstein calves given three consecutive i.m. injections of dexamethasone (DEX) (0.04 mg kg-1) showed lymphopenia and neutrophilia with increased numbers of mature neutrophils on post-injection Days 1 and 2, but these values returned to normal levels by post-injection Day 3. Interleukin-2 receptor (IL-2R) expression by peripheral blood mononuclear cells (PBMC) was evaluated by flow cytometry using a monoclonal antibody specific for bovine IL-2R alpha. Treatment with DEX significantly decreased expression of IL-2R alpha in Concanavalin A (Con A)-activated PBMC on Day 1 (P < 0.02) and on Day 2 (P < 0.1). On Day 3, expression of IL-2R alpha by PBMC was similar in control and DEX-treated calves. This decrease in IL-2R alpha expression correlated with decreased proliferative responses of PBMC to the T-cell mitogens, phytohemagglutinin (PHA) and Con A. Following in vitro treatment with recombinant human (rhu) interleukin-12 (IL-12) Con A-induced proliferative responses of PBMC tended to be higher in both groups. However, the rhu IL-12 induced increase of Con A activated proliferative responses were significantly greater in DEX-treated calves than in control calves. IL-2R alpha expression by PBMC was found to be less in calves transported 800 km in a truck as compared to that in PBMC from controls. These data suggest that stress-induced immunosuppression in calves may involve decreased IL-2R alpha expression and decreased IL-12 production. Serum chemistry results indicated a trend toward higher creatine kinase (CK) levels in DEX-treated calves. This may be due to the lysis of corticosteroid sensitive lymphocytes.
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