EXOGENOUS TESTOSTERONE (T) MODULATES TUMOR NECROSIS FACTOR-ALPHA (TNF-ALPHA) AND ACUTE PHASE PROTEINS (APP) RESPONSES TO REPEATED ENDOTOXIN (LPS) CHALLENGE IN STEERS.

Authors: Kahl, Stanislaw; Elsasser, Theodore

Submitted to: Journal of Animal Science
Publication Type: Abstract Only
Publication Acceptance Date: 5/31/2004
Publication Date: 6/1/2004
Citation: Kahl, S., Elsasser, T.H. 2004. Exogenous testosterone modulates tumor necrosis factor and acute phase protein responses to repeated endotoxin challenge in steers [abstract]. Journal of Animal Science 82(Suppl.1):180.

Interpretive Summary:

Technical Abstract: Clinical responses to some disease agents differ between sexes and this dimorphism has been attributed to the immunomodulating effects of estrogens and androgens. Our objective was to determine in steers the effect of T treatment on circulating concentrations of immune response mediators after two consecutive LPS challenges (LPS1 and LPS2, 5 d apart; 250 ng/kg BW, i.v.). Crossbred steers (n=16; 328 kg BW), fed a forage-concentrate diet to appetite, were assigned to control (C) or T treatment (n=8). Testosterone cypionate (100 mg/msq body surface, i.m.) was injected 12 and 2 d before LPS1. Mean plasma concentrations of T before LPS were 0.02 and 3.93 ng/ml (P<0.01) in C and T, respectively. For each challenge, jugular blood samples were obtained at 0, 1, 2, 4, 7, and 24 h relative to LPS injection. The response to LPS challenge was calculated as area under the time x concentration curve (AUC) for the parameter measured. After LPS1, TNF-alpha AUC was greater in T than C (3.17 vs 1.91 ng/ml x h, P<0.05). Serum Amyloid-A (SAA) and plasma haptoglobin (HG) concentrations increased (P<0.01) after LPS1 and LPS2. In all steers SAA AUC was greater after LPS1 than LPS2 (P<0.01) but the response was augmented over C with T treatment (2.70 vs 2.05 mg/ml x h, P<0.05). HG response to LPS1 within 24 h was not affected by T. However, 5 d after LPS1 mean plasma HG concentration remained higher in T than C (0.95 vs 0.27 mg/ml, P<0.01). HG response to LPS2 was greater in T than C (17.7 vs 9.7 mg/ml x h, P<0.01). Results indicate that the presence of circulating T increases the magnitude of the TNF-a response to LPS challenge as well as the subsequent increases in APP. Effects of T on increases in TNF-alpha and APP may underlie a differential presentation of disease symptoms. The data also suggest a role for T in the development of tolerance to repeated immune challenge through its effect on the increased magnitude and duration of HG response.