Background & Aims: Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis. Methods: Forty-four patients with NASH/ASH cirrhosis (decom-pensated n = 29, compensated n = 15) and nineteen controls undergoing endoscopy were recruited. Serum was obtained and LPS and LBP levels determined. Intestinal macrophages were characterized by flow cytometry, immunohistochemistry, and nitric oxide (NO) production measured in supernatant of cultured duodenal samples. Quantitative RT-PCR was performed on duo-denal biopsies assessing 84 inflammatory genes. Protein levels of cytokines/chemokines were assessed in serum and superna-tant. The duodenal wall was assessed by electron microscopy, tight junction protein expression determined by RT-PCR, immu-nohistochemistry, and Western blot and, functional analysis performed by transepithelial resistance measurement and per-meability studies. Results: Increased plasma LPS, LBP levels and higher numbers of duodenal CD33 + /CD14 + /Trem-1 + macrophages, synthesizing iNOS and secreting NO were present in decompensated cirrhosis. Upregulation of IL-8, CCL2, CCL13 at the transcriptional level, and increased IL-8, and IL-6 were detected in supernatant and serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS + and CD68 + , but not with CD11c + cells. Electron microscopy demon-strated an intact epithelial barrier. Increased Claudin-2 was detected by Western blot and immunohistochemistry, while decreased transepithelial resistance and increased duodenal per-meability were detected in decompensated cirrhosis. Conclusions: Our study shows the presence of activated CD14 +-Trem-1 + iNOS + intestinal macrophages, releasing IL-6, NO, and increased intestinal permeability in patients with cirrhosis, sug-gesting that these cells may produce factors capable of enhancing permeability to bacterial products.

Sera from 23 patients with paraneoplastic disease of the central nervous system (PNS) were examined for the presence of anti-neuronal (anti-Hu, anti-Yo/PCA) and anti-Ri) and systemic auto-antibodies, including antibodies against DNA, centromeres, nRNP, Sm antigen, Scl-70, Ro(SS-A), La(SS-B), mitochondria, thyroid antigens, parietal calls, brush border antigen and rheumatoid factor. As controls, sera from 33 patients with small cell lung cancer, 33 with ovarian cancer and 7 with breast cancer and from 107 aged-matched healthy persons were used. Systemic auto-antibodies were found in 52% of patients with paraneoplastic neurological syndromes compared with only 16% (P = 0.001) in the control group with cancer only and 15% in the group of healthy controls. The relatively high percentage of systemic auto-antibodies in patients with PNS indicates that there is a genetic susceptibility to the development of auto-immune phenomena. This may provide an explanation for the relatively rare occurrence of PNS in patients with cancer.

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