The objective of this study was to determine whether neuropeptide Y (NPY) and recombinant human interleukin-1 receptor antagonist (IL-1ra) would: first, increase food intake; secondly, decrease concentrations of GH; thirdly, reduce GHRH-induced release of GH; and fourthly, reduce changes to concentrations of IGF-I in plasma during experimental endotoxemia in sheep. Six treatments were given to six castrated male sheep in a 6x6 Latin square treatment order. Osmotic mini-pumps were implanted at 0 h and a jugular vein was cannulated. Each sheep was continuously infused with saline (0.9%) or lipopolysaccharide (LPS) (20 micrograms/kg per 24 h, s.c.) at 10 microliters/h for 72 h via the osmotic mini-pumps. Blood samples (3 ml) were collected at 15-min intervals from 24 to 33 h. At 26 h, one of three treatments (artificial cerebrospinal fluid, NPY or IL-1ra) was injected i.c.v. within 30 s (0.3 microgram/kg), then infused i.c.v. from 26 to 33 h (600 microliters/h) at 0.3 microgram/kg per h. GHRH was injected i.v. (0.075 microgram/kg) at 32 h after which blood samples were collected at 5, 10, 15, 30, 45 and 60 min. Feed intake was reduced up to 50% for 48 h in LPS-treated compared with non-LPS-treated sheep. NPY restored feed intake in LPS-treated sheep and induced hyperphagia in non-LPS-treated sheep from 24 to 48 h. In contrast, IL-1ra did not affect appetite. Injection of NPY increased concentrations of GH from 26 to 27 h, while IL-1ra had no effect. Infusion of NPY suppressed GHRH-induced release of GH. However, no treatment altered pulse secretion parameters of GH. Concentrations of IGF-I were 20% higher at 72 h in LPS-treated sheep given NPY than in sheep treated with LPS alone, and this may reflect increased appetite from 24 to 48 h. We concluded that reduced appetite during endotoxemia is due to down-regulation of an NPY-mediated mechanism. Furthermore, NPY stimulates release of GH in healthy sheep, does not reduce pulse secretion parameters of GH, but does suppress GHRH-induced release of GH in endotoxic sheep. Therefore, NPY may be an important neurotransmitter linking appetite with regulation of GH during endotoxemic and healthy states in sheep.

High doses of lipopolysaccharide (LPS) induce transient hyperglycemia, then chronic hypoglycemia and increased insulin resistance. In addition, appetite is reduced, while body temperature and concentrations of cortisol and tumor necrosis factor alpha (TNFalpha) are elevated. Furthermore, concentrations of GH and IGF-I are reduced in cattle. The objectives of this study were to determine whether a gonadal steroid implant (20 mg estrogen and 200 mg progesterone) given to endotoxemic steers would: (1) reduce hyperglycemia, reduce hypoglycemia, reduce insulin resistance, (2) reduce changes in concentrations of GH and IGF-I, (3) reduce inappetence and reduce concentrations of blood urea nitrogen (BUN) and non-esterified fatty acids (NEFA), and (4) reduce fever and concentrations of TNFalpha and cortisol. Holstein steers were assigned within a 2x2 factorial arrangement of treatments as follows (n=5 per group): C/C, no steroid and vehicle; S/C, steroid and vehicle; C/E, no steroid and LPS (1 microg/kg body weight (BW), i.v.); S/E, steroid and endotoxin. Steroid implants were given at 20 weeks of age (day 0) and serial blood samples (15 min) were collected on day 14 for 8 h, with vehicle or LPS injected after 2 h. Intravenous glucose tolerance tests (100 mg/kg BW) were carried out at 6 h and 24 h. Hyperglycemia was 67% lower (P<0.05) in S/E- compared with C/E-treated steers between 30 and 150 min after i.v. injection of LPS. Hypoglycemia developed after 4 h and insulin resistance was greater in S/E- compared with C/E-treated steers (P<0. 05) at 6 and 24 h. Concentrations of IGF-I were restored earlier in steroid-treated steers than in controls. Concentrations of GH were not affected by steroids, but increased 1 h after injection of LPS, then were reduced for 2 h. Appetite was greater (P<0.05) in S/E- (2.1% BW) compared with C/E-treated steers (1.1% BW) (pooled s.e.m.=0.3). Concentrations of NEFA increased after injecting LPS, but concentrations were lower (P<0.05) in S/E- compared with C/E-treated steers. LPS did not affect concentrations of BUN, but concentrations were lower in steroid-treated steers. Steroids did not affect body temperature or concentrations of TNFalpha and cortisol. In summary, gonadal steroids reduce hyperglycemia, reduce inappetence and tissue wasting, but increase insulin resistance. Furthermore, concentrations of IGF-I are restored earlier in steroid-treated than in non-steroid-treated steers injected with LPS. It is concluded that gonadal steroids reduce severity of some endocrine and metabolic parameters associated with endotoxemia. However, it is unlikely that gonadal steroids acted via anti-inflammatory and immunosuppressive actions of glucocorticoids or through reducing concentrations of cytokines.

Fescue toxicosis in cattle occurs as a result of consumption of ergot alkaloids in endophyte-infected (E+, Neotyphodium coenophialum) tall fescue (Festuca arundinacea). The condition is characterized by pyrexia, decreased weight gains, rough hair coats, and decreased calving rates. The objective of this experiment was to investigate whether steers grazing E+ fescue have altered host response to lipopolysaccharide (endotoxin, LPS) challenge compared with steers grazing endophyte-free (E-) fescue. Angus steers (n=8) had continuously grazed either E+ (n=4) or E- (n=4) tall fescue grass for 8 months prior to the experiment. The E+ steers had lower body weight, depressed average daily gain, and decreased basal serum prolactin compared with the E- steers prior to LPS administration. Each steer received a single bolus i.v. injection of LPS (0.2 microgram/kg body weight; Escherichia coli; 026:B6) dissolved in sterile saline, and blood was serially collected every 30 min for 4 h and at 24 h post LPS administration. LPS increased serum tumor necrosis factor-alpha (TNF-alpha), cortisol, and haptoglobin but decreased plasma glucose and IGF-I. Importantly, however, TNF-alpha, cortisol, and IGF-I responses to LPS were greater in E+ compared with E- steers. These results indicated that animals grazing E+ fescue had altered integrated metabolic host response compared with animals grazing E- fescue. Potentially, combined exposure to E+ fescue and a bacterial LPS could have greater deleterious effects on the animal compared with exposure to only one of the two and would likely lead to increased catabolism.