Tumor necrosis factor-alpha and total parenteral nutrition-induced anorexia.

BACKGROUND

We hypothesize that total parenteral nutrition (TPN) induces anorexia by an increase in anorexigenic cytokines (factors with central action via the hypothalamus) and tested this hypothesis by measuring changes in food intake and cytokines in response to TPN.

METHODS

Fischer rats with an internal jugular catheter and ad libitum food received saline solution for 10 days. On day 11, rats were randomized to TPN (G:F:AA = 50:30:20) for 4 days (days 11 through 14); control rats received on saline solution for 5 days. On day 14, one half of the TPN group was switched back to saline solution for 1 day. Daily food intake was measured. On day 14 in one half of all rats and on day 15 in the remaining, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 alpha were measured in plasma and cerebrospinal fluid (CSF). Spontaneous in vitro TNF-alpha and IL-1 alpha were also measured in peripheral blood mononuclear cells.

RESULTS

With TPN, an 80% decrease (p < 0.01) in food intake occurred; plasma TNF-alpha increased (78 +/- 9 pg/ml vs undetectable; p < 0.001), and IL-1 alpha was undetectable. Spontaneous in vitro TNF-alpha and IL-1 alpha production were unchanged. Stoppage of TPN led to return toward normal of food intake and plasma TNF-alpha. TNF-alpha and IL-1 alpha in CSF were undetectable in both groups during and after TPN.

CONCLUSION

Increase in plasma TNF-alpha with no increase in CSF-TNF-alpha during TPN, when food intake decreased, suggests an association between TPN and TNF-alpha but not necessarily cause and effect.