Effects of chronic infusion of lipopolysaccharide on food intake and body temperature of the rat

Unrestrained male Sprague-Dawley rats were infused for seven days with a low (2.45 [mu]g/hr) or high (9.81 [mu]g/hr) concentration of E. coli lipopolysaccharide (LPS). Compared to control (saline-infused) rats, food intake in the LPS-infused rats remained depressed for the entire infusion period. Despite this long-term suppression of food intake, fever was observed only during the daytime hours for the first two days of infusion. No significant increase in nighttime body temperature was observed. These data indicate that although tolerance to LPS occurred in rats with regard to its fever-inducing effect, tolerance with respect to its anorexigenic action did not occur.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27525/1/0000569.pd

Corona discharge amplification of acid group topochemistry

"May 2002."Submitted to Tappi Journal

Effect of centrally administered interleukin-1 and endotoxin on food intake of fasted rats

We have previously shown that interleukin-1 (IL-1), a polypeptide known to mediate many aspects of the acute phase response to infection, suppresses food intake when injected intraperitoneally into fasted rats. IL-1 acts at the level of the hypothalamus to induce fever. In view of the large number of peptides that have been shown to alter food intake as well as body temperature when injected intracerebroventricularly (ICV), we hypothesized that the receptor site for the anorexigenic activity of IL-1 would be located in a central nervous site bathed by the cerebrospinal fluid. In the present study, ICV injection of IL-1 or E. coli endotoxin (a stimulus for the synthesis of IL-1), significantly elevated body temperature, but did not affect food intake of fasted rats. We conclude that receptors mediating the anorexigenic actions of IL-1 or endotoxin are not located at a central nervous site bathed by the cerebrospinal fluid. Furthermore, fever per se is not reponsible for the reduction in food intake seen following peripheral injection of IL-1 or endotoxin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26437/1/0000525.pd

The effects of psychological stress on plasma interleukin-6 activity in rats

The purpose of this study was to determine the effects of a particular psychological stress, exposure to an open-field, on plasma IL-6 activity in rats. Plasma IL-6 activity was 40.6+/-7.2 units/ml in control rats, 105+/-6.8 units/ml after 30 minutes exposure to an open-field, and 221+/-17 units/ml after 60 minutes of exposure (p=0.0003). There was a positive correlation (r=.71, p=0.043) between the change in plasma IL-6 activity and body temperature. However, we conclude, based on earlier data relating plasma IL-6 activity to body temperature changes following injection of lipopolysaccharide, that the plasma levels of IL-6 following exposure to an open-field are not high enough to account for the rise in body temperature observed in rats during this stress. In conclusion, these experiments indicate that exposure to psychological stress can elevate the plasma concentration of IL-6, a known mediator of the acute phase response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28610/1/0000422.pd

Stress-induced rise of body temperature in rats is the same in warm and cool environments

Several forms of psychological stress result in a rise in body temperature in rats. In this study, we report that rats housed at a low ambient temperature (11.1[deg]C) develop stress-induced rises in body temperature that do not differ from the responses seen when the animals are kept at a temperature within their thermoneutral zone (24.7[deg]C). These data support the hypothesis that stress-induced "hyperthermia" is a regulated rise in temperature (i.e., a rise in thermoregulatory "set-point," or fever), and is not simply the result of metabolic changes associated with the stress response itself.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28659/1/0000476.pd

The effects of pentoxifylline on lipopolysaccharide (LPS) fever, plasma interleukin 6 (IL 6), and tumor necrosis factor (TNF) in the rat

The purpose of these studies was to test whether pentoxifylline, a drug that can inhibit the production and action of cytokines hypothesized to be endogenous pyrogens (for example, interleukin 1 and tumor necrosis factor [TNF]), is antipyretic. We also tested the effects of pentoxifylline on plasma activities of interleukin 6 (IL 6) and TNF in response to an injection of a fever-inducing dose of lipopolysaccharide (LPS). Our results showed that a high dose of pentoxifylline (200 mg/kg) caused hypothermia in control rats and blocked LPS fever, while a low dose (50 mg/kg) did not have these effects. Injection of the high dose of pentoxifylline in control rats caused a rise in plasma IL 6 but not in plasma TNF. However, the peak levels of plasma IL 6 and TNF activities following an injection of LPS were significantly reduced by pretreatment with pentoxifylline. Overall, the data are consistent with the hypothesis that pentoxifylline is an antipyretic drug, which may act at least in part by inhibiting the secretion of pyrogenic cytokines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28504/1/0000301.pd

Clearance of renin in unanesthetized rats: Effects of chronic lead exposure

These experiments studied the influence of chronic lead exposure on the steady-state clearance of exogenous homologous renin in unanesthetized, unrestrained rats. Relative to time controls (TC), rats chronically exposed to 500 ppm lead in drinking water had significantly elevated basal plasma renin concentrations (PRC) (Pb = 12.0 +/- 1.6 ng/ml/hr, TC = 7.6 +/- 0.8). During the infusion of homologous renin sufficient to increase plasma renin approximately 10-fold, the clearance of renin was not different between the two groups (after 60-min infusion, Pb = 16.1 +/- 1.8 ml/kg/min, TC = 15.9 +/- 1.5). Rats exposed to 1000 ppm lead did not have higher PRCs than time controls (Pb = 10.9 +/- 2.2, TC = 9.2 +/- 1.8). The clearances of renin in these two groups were also not significantly different (Pb = 15.3 +/- 2.8, TC = 18.3 +/- 2.5). Renal renin concentrations were significantly elevated in the 500 ppm rats (Pb = 1426 +/- 110 ug/kidney, TC = 1065 +/- 118) consistent with an increased basal renin secretion, but were not elevated in the 1000-ppm rats. There were no significant differences in the clearances of sulfobromophthalein (BSP) between any of the groups. The renin infusion significantly reduced BSP clearance, but did so equally in all groups. It is concluded that in unanesthetized, unrestrained rats the clearance of renin is not altered by chronic lead exposure of either 500 or 1000 ppm and that increased secretion of renin accounts for the elevated basal PRC observed in rats exposed to the lower dose of lead.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25186/1/0000625.pd

A theoretical mode of action of aldosterone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32373/1/0000448.pd

Hyperthermia induced by open-field stress is blocked by salicylate

Psychological stress results in a rise in body temperature. Here we report that in rats, hyperthermia induced by open-field stress can be blocked by administration of the antipyretic drug sodium salicylate. These data suggest that this rise in body temperature is a true fever, perhaps mediated by prostaglandins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26453/1/0000541.pd

Further evidence that stress hyperthermia is a fever

Exposure of rats to an open-field results in a rapid rise in body temperature. Fifty-four percent of this rise in body temperature was blocked by intracerebroventricular administration of the antipyretic drug sodium salicylate. Intraperitoneal administration of indomethacin, a potent blocker of prostaglandin production, also attenuated the stress-induced hyperthermia to the same degree. Based on the data presented in this and an earlier study, we conclude that a major component of the rise in body temperature induced by psychological stress in rats is mediated by prostaglandins released by the central nervous system, and may therefore be a fever.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26990/1/0000557.pd