Effect of intracerebroventricular injection of tumor necrosis factor alpha on gut mucosal protein turnover in mice fed enterally.

OBJECTIVE

The objective of this study was to determine whether mucosal protein turnover is enhanced by intracerebroventricular (ICV) injection of tumor necrosis factor alpha (TNF-alpha) in mice fed enterally.

METHODS

Male B6C3F1 mice (n = 37, 20.0-25.0 g) were catheterized in the ICV space using stereotaxic coordination, and subsequently a catheter was inserted into the stomach for enteral feeding on Day 0. The animals were fed a standard mouse diet and water ad libitum for 4 days. On Day 4, enteral feeding was begun with a standard liquid diet, and either artificial cerebrospinal fluid (control) or recombinant human (Rh) TNF-alpha (5 ng/h) was continuously given via the ICV catheter using an osmotic pump. On either Day 5 or 7, the mice were sacrificed 10 min after injection of [U-(14)C]phenylalanine (5 microCi/mouse, ip). Fractional synthetic rates (FSRs) of jejunal mucosa and muscle were measured by the pool flooding technique. Interleukin-6 (IL-6) levels in the plasma were measured by ELISA.

RESULTS

Body weight was significantly reduced by ICV injection of TNF-alpha, because muscle FSR was decreased with TNF-alpha. There were no differences in IL-6 levels in the plasma between the two groups. The FSR of jejunal mucosa was elevated by infusion of TNF-alpha as compared with control mice on both Days 5 and 7 [Day 5: (control) 99.5 +/- 17. 6%/day vs (TNF) 150.5 +/- 20.5%/day, P < 0.05; Day 7: (control) 54.8 +/- 8.8%/day vs (TNF) 102.7 +/- 19.1%/day, P < 0.05).

CONCLUSION

injection of TNF-alpha enhanced the mucosal protein synthesis rate without elevating IL-6 levels as compared with control mice, suggesting that the central nervous system links to the gut to regulate mucosal protein turnover through cytokine in the brain, but plasma IL-6 is not involved in this linkage.