Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several thousand-fold in human sepsis, and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin I gene (CALC I) expression in human adipocyte primary cultures and in adipose tissue samples from infected and noninfected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, the expression of CT mRNA increased 24-fold (P < 0.05) after the administration of Escherichia coli endotoxin (lipopolysaccharide) and 37-fold (P < 0.05) after IL-1beta administration by 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with lipopolysaccharide treatment and 15.2-fold (P < 0.01) with IL-1beta after 48 h. In coculture experiments, adipocyte CT mRNA expression was evoked by E. coli-activated macrophages in which CT mRNA was undetectable. The marked IL-1beta-mediated ProCT release was inhibited by 89% during coadministration with interferon-gamma (IFNgamma). In patients with infection and markedly increased serum ProCT, CT mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFNgamma on IL-1beta-induced CT mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.

The morbidity after SLN biopsy alone is not negligible but significantly lower compared with level I and II ALND. SLN biopsy can be performed with similar short- and intermediate-term morbidity in academic and nonacademic centers.

The response to partial hepatectomy (PH) is impaired in interleukin 6 (IL-6)-deficient mice. IL-6 is well known for its role in the induction of the acute phase (AP) response, and the impairment of this response after surgery and hepatectomy could explain the defective hepatocyte regeneration. In addition, it was proposed that IL-6 has an important role in stimulating the reentry of quiescent cells into the cell cycle within the first 2 to 4 hours after PH. To further analyze the role for IL-6, we performed two third hepatectomies in wild-type mice, in IL-6 knockout (KO) mice, and in IL-6 KO mice that were treated 30 minutes before surgery with intravenous (IV) (short acting) or subcutaneous (SC) (long acting) injections of recombinant IL-6. The high postoperative mortality of IL-6 -deficient mice could be completely prevented by SC, but not by IV IL-6 treatment, showing the requirement of a sustained action of IL-6. However, there is a subset of IL-6 KO mice that survives a PH in good health even without IL-6 treatment. When we analyzed these mice, we found an intact liver regeneration and no indication of a block in cell cycle reentry. We conclude that the major role of IL-6 is the induction of an adaptive response to PH that ensures body homeostasis and survival. (HEPATOLOGY 2003;38:674-682.)

STOECKLI, ROLF, ROBIN CHANDA, IGOR LANGER, AND ULRICH KELLER. Changes of body weight and plasma ghrelin levels after gastric banding and gastric bypass. Obes Res. 2004;12:346 -350. Objective: Ghrelin is an enteric peptide with strong orexigenic and adipogenic effects. Plasma ghrelin levels are decreased in obese subjects but increase after weight loss; this increase is not observed after Roux-en-Y gastric bypass (RYGB). Prospective and comparative data after adjustable silicone gastric banding (ASGB) have not been reported previously. Research Methods and Procedures:Overnight fasting plasma ghrelin concentration was measured in morbidly obese subjects at baseline and 3, 6, 12, and 24 months after ASGB (n ϭ 8) or RYGB (n ϭ 5) and in nonoperated controls (n ϭ 7). Results: After RYGB, body weight (BW) decreased by 29.5 Ϯ 5.5 kg (mean Ϯ SE, p Ͻ 0.001), whereas plasma ghrelin failed to increase significantly (ϩ167 Ϯ 119 pg/mL, not significant). In contrast, after ASGB, BW decreased less (by 22.8 Ϯ 5.9 kg; p Ͻ 0.001), and plasma ghrelin significantly increased by 377 Ϯ 201 pg/mL (p ϭ 0.025). Neither BW nor plasma ghrelin changed in nonoperated controls. Plasma leptin decreased in both operated groups (similarly p Ͻ 0.05) but not in nonoperated controls. Plasma growth hormone and insulin-like growth factor 1 were not correlated with changes in plasma ghrelin concentrations.Discussion: Plasma ghrelin levels failed to increase during substantial weight loss after RYGB, but did increase in response to lesser weight loss after ASGB. These findings suggest that the plasma ghrelin response after weight loss is impaired after exclusion of major parts of the stomach and the duodenum (RYGB), and the smaller long-term weight loss after ASGB compared with RYGB may be due, at least in part, to an absent increase in plasma ghrelin after RYGB.

No abstract