Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/15/2003
Publication Date: 10/20/2003
Citation: Eicher, S.D., Mcmunn, K.A., Hammon, H.M., Donkin, S.S. 2003. Toll-like receptors 2 and 4, and acute phase cytokine gene expression in dexamethasone and growth hormone treated dairy calves. Veterinary Immunology And Immunopathology. V. 98. P. 115-125. Interpretive Summary: Toll-like receptors are cell surface molecules that recognize and differentiate harmful particles (pathogens), including bacteria and virus. The toll-like receptors then initiate an appropriate immune response resulting in production of cell signaling proteins (acute phase cytokines) that direct the early response to pathogens. Cattle that are exposed to stimulants of growth hormone and to stressors that cause stress-hormone release may have altered expression and function of the toll-like receptors (TLR) and acute phase cytokines. The objective of this study was to determine changes in two toll-like receptors (TLR2 and TLR4) and two early cell signals (cytokines; interleukin-1 and tumor necrosis factor-")following treatment with a synthetic stress hormone and growth hormone. The greatest change in TLR2 and the cytokines that it stimulates occurred in cells from the lungs. A large increase was observed by day 56 for calves that were receiving both hormones. However, the other toll-like receptor (TLR4) was not altered by the treatments. Immune cells from the blood showed some altered cytokine responses and early (day 14) changes in both toll-like receptors. These data showed that toll-like receptors in cattle can be altered by hormone treatments, which may alter resistance to disease. These data suggest, that during periods of stress the addition of GH may be harmful to calves. This finding will initiate research in the area of toll-like receptor modulation of the immune status of cattle, and indicates to producers how stimulating the hormones together may be detrimental.
Technical Abstract: Cattle that are exposed to growth hormone stimulants and to stressors that cause cortisol release may have altered immune responses, reducing resistance to disease. Toll-like receptors and acute phase cytokines direct the early response to pathogens. The objective of this study was to determine changes in toll-like receptors (TLR)and acute phase cytokines following treatment with a synthetic glucocorticoid (dexamethasone) and growth hormone (GH). Twenty eight calves were given the control (Cnt), dexamethasone (DEX),GH, or DEX and GH (Both) treatments from 3 d-of-age until 56 d-of age. Blood was collected on d 14, 28, 42, and 56. Calves were exsanguinated on d 56, a lung lavage was performed and spleen and thymus tissues collected. Total RNA was extracted from blood leukocytes, lung lavage cells, spleen, and thymus cells. Real-time RT-PCR was used to quantify Interleukin-1(IL-1), IL-1 Receptor antagonist (IL-1Ra), TNF-alpha, TLR2, and TLR4. Blood leukocytes had a time effect for IL-1 Ra (P<.01)and a treatment by time interaction (P<.05), but IL-1, TNF, and TLR2 and 4 were not different among treatments nor over time. IL-1 expression of lung lavage cells was greatest (P<.05) for calves on the Both treatment (2.58, 5.62, 3.64, and 22.53 for Cnt, DEX, GH, and Both). TLR2 expression was enhanced with Both compared to either DEX or GH (P<.05). Tumor necrosis factor-alpha was greatly enhanced by Both compared to the other three treatments (P<.05). Spleen cell TNF-alpha expression was enhanced by the DEX treatment alone compared to the GH treatment (7.14 and 4.46; P<.05). No differences were seen in thymus cell expression. These data demonstrate that TLR2 and TLR4 and acute phase cytokine expression can be altered by stress and growth hormones, which may alter resistance of those animals to disease.