Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis.

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas).

Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice.

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups.

Mechanism of sustained E-selectin expression in cultured human dermal microvascular endothelial cells.

Persistent E-selectin expression has been proposed to be a unique property of dermal vascular endothelium that directs skin-specific homing of a subpopulation of circulating memory T cells. We compared the kinetics of E-selectin expression on cultured human dermal microvascular endothelial cells (HDMEC) with expression on HUVEC. Following treatment with TNF, E-selectin on HDMEC appears more slowly than on HUVEC (peak values 6-8 vs 4 h, respectively) and is sustained at significantly higher levels after 24 h.

IL-1 type I receptor mediates acute phase response to turpentine, but not lipopolysaccharide, in mice.

This study examined the role of the interleukin-1 (IL-1) type I receptor (IL-1RtI) in the acute phase response (APR) to inflammation in mice. Turpentine (100 microliters/mouse) injected subcutaneously induced fever, lethargy, body weight loss, and anorexia in IL-1RtI wild-type mice. Knockout mice lacking the IL-1RtI were resistant to these effects of turpentine, supporting a role for this receptor in the APR to local inflammation.

The CNS site of glucocorticoid negative feedback during LPS- and psychological stress-induced fevers.

Glucocorticoids exert negative feedback in the anterior hypothalamus (AH) during lipopolysaccharide (LPS)-induced fevers, but the central location of their negative feedback during psychological stress-induced fever has not been determined. To confirm that glucocorticoid modulation of LPS fever occurs in the AH, adrenalectomized animals were injected intrahypothalamically with either 0.25 ng of corticosterone or vehicle followed by 50 micrograms/kg LPS intraperitoneally.

Hemorrhage suppresses fever, interleukin-6, and tumor necrosis factor-alpha responses to lipopolysaccharide in rats.

The purpose of this study was to test the hypothesis that attenuation of the fever response to lipopolysaccharide (LPS) following hemorrhage is accompanied by changes in serum glucocorticoid levels and a decreased bioactivity of TNF-alpha and IL-6 in plasma. Hemorrhage was induced in rats by the withdrawal of 20% of estimated total blood volume. LPS (50 microg/kg) or saline were injected intraperitoneally immediately after the hemorrhage.

Beta-adrenoceptor antagonists suppress elevation in body temperature and increase in plasma IL-6 in rats exposed to open field.

The purpose of these studies was to assess the involvement of beta-adrenoceptors in the development of psychological stress-induced elevation in body temperature (Tb) and rise in circulating interleukin-6 (IL-6). We selected three drugs to attempt to block the rise in body temperature and plasma IL-6; L-propranolol, D-propranolol and nadolol. Both stereoisomers of propranolol have "local anesthetic' membrane-stabilizing activity and are capable of penetrating into the brain.

The adaptive value of fever.

There is overwhelming evidence in favor of fever being an adaptive host response to infection that has persisted throughout the animal kingdom for hundreds of millions of years. As such, it is probable that the use of antipyretic/anti-inflammatory/analgesic drugs, when they lead to suppression of fever, results in increased morbidity and mortality during most infections; this morbidity and mortality may not be apparent to most health care workers because fever is only one of dozens of host defense responses. Furthermore, most infections are not life-threatening and subtle changes in morbidity are not easily detected.

Life-sustaining treatment decisions by spouses of patients with Alzheimer's disease.

Objective: To examine the anticipated decisions to consent to or to forgo life-sustaining treatment by spouses of patients with Alzheimer's disease and to describe the relationship of spouse and patient characteristics to predicted decisions.

Design: Prospective quantitative study.

Setting: The Aging and Dementia Research Center (ADRC), part of an Alzheimer's Disease Center Core Grant, at New York University Medical Center.

The effect of oral cisapride premedication on fasting gastric volumes.

The aim of this study was to determine whether fasting gastric volumes could be reduced by preoperative administration of cisapride. One hundred and twenty-one patients undergoing elective general anaesthesia were randomly allocated to receive either cisapride 20 mg plus diazepam 10 mg or placebo tablets plus diazepam 10 mg, two hours prior to induction. Immediately following induction blind gastric aspiration was performed using a 16Fr multiorificed orogastric tube.

Thermal and behavioral effects of lipopolysaccharide and influenza in interleukin-1 beta-deficient mice.

This study characterized body temperature (Tb), locomotor activity (Act), and feeding behavior under normal conditions and following injection with lipopolysaccharide (LPS) or inoculation with live influenza virus of transgenic C57/black mice deficient in interleukin-1 beta (IL-1 beta). Tb and Act in freely moving mice were measured by biotelemetry. Mice deficient in IL-1 beta had normal circadian rhythm of Tb but were less active than their control counterparts.

Body temperature, motor activity, and feeding behavior of mice treated with beta-chlornaltrexamine.

The effects of an irreversible long term opioid antagonism on circadian rhythms in body temperature (Tb), locomotor activity (Act) and feeding under normal conditions and following lipopolysaccharide administration (LPS; 2.5 mg/kg) have been investigated in unrestrained mice housed at their thermoneutral zone (30 degrees C). beta-chlornaltrexamine (beta-CNA; 5 mg/kg) given intraperitoneally decreased Tb on the day of injection, depressed Act, and reduced food and water intake for several days.

Cytokines and fever.

Fever is an excellent example of neuroimmunomodulation in that mediators of immunity initiate a pathway to raise the thermoregulatory set-point, resulting in behavioral and physiological responses that increase body temperature. This rise in temperature is thought to be adaptive, facilitating host defenses. Many cytokines are endogenous mediators of fever (i.

TNF soluble receptor and antiserum against TNF enhance lipopolysaccharide fever in mice.

We tested the effects of tumor necrosis factor (TNF) soluble receptor (sTNFR) and anti-TNF serum (anti-TNF) administered intraperitoneally on fever induced by lipopolysaccharide (LPS) in mice. Both agents have been shown to block bioactivity of mouse TNF-alpha. Core temperature (Tb) and locomotor activity in unrestrained mice were measured by biotelemetry.

Role of epinephrine in TNF and IL-6 production from isolated perfused rat liver.

A bidirectional communication exists between the nervous system and the immune system. Evidence has accumulated suggesting that cytokines-immune peptides influence sympathetic neuronal survival and that cytokines can promote the secretion of catecholamines. Using an isolated perfused rat liver (IPRL) preparation, we have shown that the liver is an important source of circulating cytokines in response to lipopolysaccharide (LPS) and that corticosterone dose dependently influenced LPS-induced production of tumor necrosis factor (TNF) and interleukin-6 (IL-6).

Role of corticosterone in TNF and IL-6 production in isolated perfused rat liver.

Using an isolated perfused rat liver (IPRL) preparation, we assessed whether corticosterone may contribute to the rise in tumor necrosis factor (TNF) and interleukin-6 (IL-6) in rats after injection with lipopolysaccharide (LPS) or exposure to psychological stress. Intravenous infusion of LPS into the IPRL led to dose-dependent increases in TNF and IL-6 concentrations in the effluent. Anisomycin, a protein synthesis inhibitor, completely blocked the rise in TNF and IL-6 concentration in the IPRL effluent, supporting the hypothesis that the synthesis (or release) of these cytokines was dependent on protein synthesis.

Systemic but not central administration of tumor necrosis factor-alpha attenuates LPS-induced fever in rats.

The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 microgram) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.

Effect of voluntary exercise and food restriction in response to lipopolysaccharide in hamsters.

We tested the hypothesis that voluntary running and moderate food restriction alter the acute phase response (APR), one index of nonspecific immune function. Hamsters were kept sedentary or permitted to run and were fed ad libitum or had food restricted for 20 days and were then injected intraperitoneally with saline or lipopolysaccharide (LPS). Fever and circulating interleukin-6, serum amyloid A (SAA), serum iron, and cortisol were measured by biotelemetry, B-9 cell growth assay, indirect enzyme-linked immunosorbent assay, colorimetric analysis, and radioimmunoassay, respectively.

Effect of exercise and food restriction on selected markers of the acute phase response in hamsters.

Acute aerobic exercise has been shown to elicit physiological changes characteristic of the acute phase response (APR), a nonspecific host defense response. Regular evocation of these changes may prime the immune system to improve resistance to disease. Because food deprivation is associated with an impaired APR, food restriction may prevent these beneficial changes.

Cytokines and the acute phase response to influenza virus in mice.

This study characterized selected aspects of the acute phase response after intranasal inoculation of mice with two doses of mouse-adapted influenza virus differing in lethality. Mice given 140 plaque-forming units (PFU) of virus (58% survival) gradually decreased food and water intake to nearly zero over 6 days; survivors then slowly increased intakes. Declines in these behaviors were parallel to decreases in body temperature and general locomotor activity and were associated with elevated activities of interleukin-6 (IL-6), tumor necrosis factor-alpha, and interferons in lung lavage fluid.

Development of altered taste preferences in tumor-bearing rats.

Experimental tumors induce a decline in food intake that may derive from changes in taste or the development of taste aversions. The preferences of tumor-bearing (TB) and non-tumor-bearing (NTB) rats for five chemicals (three palatable and two aversive taste stimuli) were studied in an animal model of experimental cancer employing the methylcholanthrene (MCA) sarcoma. In protocol 1, five groups of Fischer 344 rats were given 23-h, two-bottle preference tests (taste solution vs.

Regulation of scatter factor production via a soluble inducing factor.

Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a fibroblast-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. SF may play major roles in development, repair, and carcinogenesis. However, the physiologic signals that regulate its production are not well delineated.