Peripheral administration of
interleukin-1 (IL-1) reduces food intake and affects brain serotonergic activity, suggesting a causal relationship. Furthermore,
IL-1 increases the brain concentrations of the
serotonin precursor,
tryptophan (TRP), by unclear mechanism(s). We aimed at confirming the link between
IL-1 administration, raised brain TRP concentrations and the development of
anorexia, and at investigating the mechanisms of TRP entry into the brain. Thirty adult, overnight fasted Sprague-Dawley rats were randomly assigned to i.p.
injections of 1 mug/kg BW of
IL-1 alpha (n=10) or vehicle (n=10), or to pair-feeding with
IL-1 animals (n=10). After 2 h, food intake, blood plasma concentrations of total TRP, free TRP, large
neutral amino acids (LNAA; competing with TRP for brain entry) were measured. Cerebral spinal fluid (CSF) TRP concentrations were also measured. TRP brain availability was assessed by calculating the plasma ratio free TRP/LNAA. Following
IL-1 injection, food intake significantly declined in
IL-1 rats, which was paralleled by decreased plasma free TRP and increased plasma LNAA. Despite a decrease in the free TRP/LNAA ratios in plasma,
IL-1 significantly increased concentrations of TRP in CSF. These data show that the acute peripheral administration of
IL-1 induces
anorexia and raises CSF TRP levels. Considering the possible role of the raised CSF TRP in influencing brain
serotonin activity, it is postulated that increased serotonergic neurotransmission could be involved in
IL-1 induced
anorexia.