|Kahl, Stanislaw - Stass|
Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2005
Publication Date: 12/7/2005
Citation: Kahl, S., Elsasser, T.H. 2005. Exogenous testosterone modulates tumor necrosis factor-A and acute phase proteins responses to repeated endotoxin challenge in steers. Domestic Animal Endocrinology. Available:http://dx.doi.org/doi:10.1016/j.domaniend.2005.11.005 Interpretive Summary: Disease responses of animals affect some animals more than others. In particular, it has been recognized that males and females are affected differently in terms of how severe they respond to inflammatory stress. We did an experiment to determine whether testosterone might play a role in modulating aspects of the inflammatory response to an immune challenge. Beef steers were treated or not treated with a long-acting testosterone preparation to achieve in the steers plasma testosterone levels equivalent to those measurable in bulls. Upon challenge with the bacterial extract called endotoxin, animals receiving the testosterone had increased cytokine production and prolonged increases in liver proteins that suggest the testosterone may have boosted some aspects of the inflammatory response to the endotoxin. Knowing where in the pathway of responses testosterone has an effect may aid animal scientists to develop simple strategies to increase the health status of cattle.
Technical Abstract: Clinical responses to some disease agents differ between sexes and this dimorphism has been attributed to the immunomodulating effects of steroid hormones. Our objective was to determine in steers the effect of testosterone on circulating concentrations of immune response mediators after two consecutive endotoxin challenges (LPS1 and LPS2, 5 days apart; 0.25 µg/kg BW). Sixteen crossbred steers (328 ± 6 kg) were assigned to control (CON, n = 8) or testosterone cypionate treatment (TES; 100 mg/m2 body surface; i.m. injection 12 and 2 days before LPS1). The response to LPS challenge was calculated as area under the time × concentration curve (AUC) for the parameter measured. After LPS1, tumor necrosis factor-a AUC was greater in TES than CON (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 CON with TES treatment (P < 0.05). HG response to LPS1 within 24 h was not affected by testosterone. However, 5 days after LPS1 mean plasma HG concentration remained higher in TES than CON (P < 0.01). HG response to LPS2 was greater in TES than CON (P < 0.01). Results indicate that the presence of circulating testosterone increases the magnitude of the TNF-a response to LPS challenge as well as the subsequent increases in acute phase proteins (APP). Effects of testosterone on increases in TNF-' and APP may underlie a differential presentation of disease symptoms. The data also suggest a role for testosterone in the development of tolerance to repeated immune challenge through its effect on the increased magnitude and duration of HG response.