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This study examined the effects of endotoxin administration on food and water consumption in humans, and the associations between these changes and endotoxin-induced secretion of cytokines, cortisol, and fever. Twenty healthy male volunteers received an i.v. injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in two experimental sessions. Blood samples were collected hourly, and rectal temperature was monitored continuously. Food consumption was significantly reduced at 0-4 h and significantly elevated at 4-5 h after the endotoxin injection. Endotoxin administration had no significant effect on water consumption. Endotoxin-induced secretion of TNF-alpha and IL-6 was positively associated with the decrease in food consumption (r=0.61 and 0.68), and negatively associated with the rebound increase in food consumption (r=-0.53 and -0.45). Neither the febrile response, nor the secretion of cortisol was associated with the changes in food consumption. These results suggest that TNF-alpha and IL-6 are involved in endotoxin-induced anorexia in humans.

Recent findings suggest that inflammatory cytokines are involved in sleep regulation. In part, this idea is based on studies showing that systemic levels of interleukin-6 (IL-6) are affected by sleep and sleep deprivation. However, intravenous (IV) catheters used for repetitive blood sampling were reported to increase local IL-6 production, which might confound sleep-dependent or circadian changes in the plasma concentrations of this cytokine. To further examine the effects of blood drawing procedures on IL-6 plasma levels, 12 healthy young male subjects participated in a 24-h cross-over study protocol involving sleep and sleep deprivation. Blood was collected half-hourly through an IV line and one additional sample was taken by a simple needle stick from the contralateral arm in parallel to the last sample from the catheter. Difficulties in blood sampling, the plasma levels of IL-6, cortisol and subjective sleepiness were quantified. In samples from the IV line there was a linear increase in IL-6 levels in both conditions, whereas the amount of IL-6 detected in the needle stick sample at the end did not differ from baseline. IL-6 levels were significantly higher in samples rated as difficult and those difficulties were more frequent during sleep compared to nocturnal wakefulness. IL-6 levels did not correlate to variations in sleepiness or cortisol levels. We conclude that variations in IL-6 plasma levels measured in samples from an IV catheter are caused, at least in part, by changes in local cytokine production rather than by physiological changes in circulating IL-6 levels.