Possible anti-inflammatory role of Zingiberis processum rhizoma, one component of the Kampo formula daikenchuto, against neutrophil infiltration through muscarinic acetylcholine receptor activation.

Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatory action by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatory action via a reduction of neutrophil infiltration against postoperative ileus (POI). In this study, we orally administered individual herbal components of DKT to mice four times before and after intestinal manipulation (IM). The anti-inflammatory action of each crude drug was evaluated by histochemical analysis of relevant molecules. The results showed that treatment with all herbal components of DKT significantly inhibits neutrophil infiltration. This inhibition of neutrophil infiltration by ZPR was significantly reduced in 5-hydroxytryptamine receptor 4 (5-HT4R) knockout (KO) mice but not in alpha-7 nicotinic acetylcholine receptor (α7nAChR) KO mice. Also, transient receptor potential ankyrin 1 (TRPA1) and muscarinic acetylcholine receptor (mAChR) antagonists partly and significantly inhibited the amelioration of neutrophil infiltration by ZPR. Therefore, DKT-induced anti-inflammatory action, mediated by inhibition of neutrophil infiltration in POI, depends, in part, on the effects of ZPR. ZPR activates TRPA1 channels, possibly in enterochromaffin (EC) cells, to release 5-HT. This 5-HT stimulates 5-HT4R in the myenteric plexus neurons to release acetylcholine, which, in turn, activates mAChR to inhibit inflammation in POI.

A role for 12/15-lipoxygenase-derived proresolving mediators in postoperative ileus: protectin DX-regulated neutrophil extravasation.

Resolution of inflammation is an active counter-regulatory mechanism involving polyunsaturated fatty acid-derived proresolving lipid mediators. Postoperative intestinal motility disturbances, clinically known as postoperative ileus, occur frequently after abdominal surgery and are mediated by a complex inflammation of the intestinal muscularis externa. Herein, we tested the hypothesis that proresolving lipid mediators are involved in the resolution of postoperative ileus. In a standardized experimental model of postoperative ileus, we detected strong expression of 12/15-lipoxygenase within the postoperative muscularis externa of C57BL/6 mice, predominately located within CX3CR1(+)/Ly6C(+) infiltrating monocytes rather than Ly6G(+) neutrophils. Mass spectrometry analyses demonstrated that a 12/15-lipoxygenase increase was accompanied by production of docosahexaenoic acid-derived lipid mediators, particularly protectin DX and resolvin D2, and their common precursor 17-hydroxy docosahexaenoic acid. Perioperative administration of protectin DX, but not resolvin D2 diminished blood-derived leukocyte infiltration into the surgically manipulated muscularis externa and improved the gastrointestinal motility. Flow cytometry analyses showed impaired Ly6G(+)/Ly6C(+) neutrophil extravasation after protectin DX treatment, whereas Ly6G(-)/Ly6C(+) monocyte numbers were not affected. 12/15-lipoxygenase-deficient mice, lacking endogenous protectin DX synthesis, demonstrated increased postoperative leukocyte levels. Preoperative intravenous administration of a docosahexaenoic acid-rich lipid emulsion reduced postoperative leukocyte infiltration in wild-type mice but failed in 12/15-lipoxygenase-deficient mice mice. Protectin DX application reduced leukocyte influx and rescued 12/15-lipoxygenase-deficient mice mice from postoperative ileus. In conclusion, our results show that 12/15-lipoxygenase mediates postoperative ileus resolution via production of proresolving docosahexaenoic acid-derived protectin DX. Perioperative, parenteral protectin DX or docosahexaenoic acid supplementation, as well as modulation of the 12/15-lipoxygenase pathway, may be instrumental in prevention of postoperative ileus.

Transcutaneous electrogastrography in patients with ileus. Relations to interleukin-1beta, interleukin-6, procalcitonin and C-reactive protein.

BACKGROUND: The aim of the prospective study was to characterize the disturbance of gastric electrical control activity in different types of ileus and to correlate surface electrogastrography (EGG) findings with a set of inflammatory markers. PATIENTS AND METHODS: Fifty-four adult patients with mechanic, vascular and paralytic ileus proven on clinical and radiological exams and 14 age- and sex-matched controls were examined. Gastric myoelectrical activity was recorded using 3 Ag-AgCl disposable skin electrodes connected in pseudo-unipolar mode by Microdigitrapper device. The captured signal was amplified and digitalized. The dominant frequency was calculated using computerized algorithms (Fast Fourier transform and running spectrum analysis). The results were correlated with the known pathological diagnoses and 4 inflammatory parameters--interleukin (IL)-1beta, IL-6, procalcitonin (PCT) and C-reactive protein. RESULTS: Irregular EGG activity without a dominant frequency or bradygastria (electrical control activity frequency <2.4 cycles/min) was seen in all patients with both vascular and parayltic ileus and in 67.86% of the patients with obstructive ileus. Normogastria (2.4-3.7 cycles/min) was found in 32.14% of the patients with obstructive ileus. Among the patients with obstructive ileus and bradygastria, higher concentrations of IL-6 (642.0 +/- 214.7 ng/l) and PCT (0.93 +/- 0.22 microg/l) were observed compared with the patients with normogastria--IL-6 (354.5 +/- 109.2 ng/l), PCT (0.69 +/- 0.11 microg/l); p < 0.05 for both. The C-reactive protein concentration did not differ in both subgroups on p < 0.05. CONCLUSIONS: EGG examination confirmed a high sensitivity in the evaluation of gastric electrical control activity in both vascular and paralytic ileus. Significant correlation of EGG findings and both IL-6 and PCT plasma levels supports a role of the inflammatory milieu in the pathogenesis of impaired gastric electrical activity in patients with ileus.