Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease.

Endothelial cells, by virtue of their capacity to express adhesion molecules and cytokines, are intricately involved in inflammatory processes. Endothelial cells have been shown to express interleukin-1 (IL-1), IL-5, IL-6, IL-8, IL-11, IL-15, several colony-stimulating factors (CSF), granulocyte-CSF (G-CSF), macrophage CSF (M-CSF) and granulocyte-macrophage CSF (GM-CSF), and the chemokines, monocyte chemotactic protein-1 (MCP-1), RANTES, and growth-related oncogene protein-alpha (GRO-alpha). IL-1 and tumor necrosis factor-alpha (TNF-alpha) produced by infiltrating inflammatory cells can induce endothelial cells to express several of these cytokines as well as adhesion molecules. Induction of these cytokines in endothelial cells has been demonstrated by such diverse processes as hypoxia and bacterial infection. Recent studies have demonstrated that adhesive interactions between endothelial cells and recruited inflammatory cells can also signal the secretion of inflammatory cytokines. This cross-talk between inflammatory cells and the endothelium may be critical to the development of chronic inflammatory states. Endothelial-derived cytokines may be involved in hematopoiesis, cellular chemotaxis and recruitment, bone resorption, coagulation, and the acute-phase protein synthesis. As many of these processes are critical to the maturation of an inflammatory and reparative state, it appears likely that endothelial-derived cytokines play a crucial role in several diseases, including atherosclerosis, graft rejection, asthma, vasculitis, and sepsis. Genetic and pharmacologic manipulation of endothelial-derived cytokines provides an additional approach to the management of chronic inflammatory diseases.

Prevalence of Helicobacter pylori infection in patients with reflux oesophagitis.

In this prospective study 30 patients of reflux esophagitis were studied to detect if there was any association between presence of esophagitis and H. pylori infection. 30 patients of non-ulcer dyspepsia acted as controls. In both the groups esophageal and antral biopsies were studied for the presence of H. pylori infection. None of the esophageal biopsies showed H. pylori infection in either group. H. pylori positivity was similar in the antrum of the patients with esophagitis (20 out of 30) and non ulcer dyspepsia (19 out of 30) (p > 0.05). There was no significant association between presence of H. pylori infection in antrum and severity of esophagitis (p > 0.05). In conclusion, this study has shown that H. pylori did not colonise esophagus in patients of esophagitis or patients of non-ulcer dyspepsia. There was no significant association between H. pylori colonization in the antrum and esophagitis and the grade of esophagitis with H. pylori infection.

Multifunctional cytokine expression by human coronary endothelium and regulation by monokines and glucocorticoids.

Human endothelium is capable of expressing a variety of molecules, including cytokines and growth factors, critical to inflammation. This aspect of coronary endothelium has not been studied in detail. In this study, we report, for the first time, expression of multifunctional cytokines by human coronary artery endothelial cells (HCAEC) and their regulation by inflammatory cytokines and glucocorticoids. We also compared expression of cytokine transcripts in two additional cell lines derived from pulmonary artery (HPAEC) and umbilical vein (HUVEC) endothelium. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction of IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and MCP-1 was seen following treatment with TNFalpha. We found no expression of IL-1RA, IL-2, IL-4, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1beta and TNF-alpha synergistically induced IL-6 and GM-CSF and additively induced IL-8 and MCP-1 production, while IL-2, IL-10, IFN-alpha, and IFN-gamma had little or no additional effects. Interestingly, no IL-1alpha or IL-5 protein product was found even after maximal stimulation of HCAEC. No significant differences were seen in the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC. Glucocorticoids inhibited IL-8 production from all three cell lines. This study demonstrates that human coronary endothelial cells are capable of expressing a wide variety of multifunctional cytokines which may be of relevance to vascular inflammation.

Primary breast cancer in aberrant breast tissue in the axilla.

Primary breast cancer in aberrant axillary breast tissue is rare. Breast cancer in the axilla is most often due to lymph node metastases from an ipsilateral breast tumor or from an occult primary lesion. We describe two patients with primary breast cancer in aberrant breast tissue in the axilla, and review the literature to define guidelines for diagnosis and treatment.