Interleukin-8. A corneal factor that induces neovascularization.

A rabbit corneal pocket model was used to demonstrate that physiologic concentrations of human recombinant (r) IL-8 may induce corneal neovascularization. Computer-assisted analysis of sequential fluorescein angiograms showed that rIL-8 doses ranging from 2 to 40 ng/cornea (P = 0.01), but not high dose rIL-8 (400 ng/cornea), results in neovascularization within 14 days.

Expression and regulation of human pulmonary fibroblast-derived monocyte chemotactic peptide-1.

Monocyte recruitment is essential for maintenance of normal pulmonary macrophage populations. In addition, acute and chronic inflammatory pulmonary diseases are associated with sequestration of mononuclear phagocytes in the lung. Although alveolar macrophages (AM phi) can secrete a number of potent inflammatory and chemoattractment mediators, these immune cells do not produce monocyte chemotactic peptide (MCP-1) in response to lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin-1 beta (IL-1 beta).

The detection of a novel neutrophil-activating peptide (ENA-78) using a sensitive ELISA.

Neutrophil elicitation into tissue is an essential element of the host defense in response to various stimuli, including, tissue injury, infection, or cancer. This event has gained renewed interest with the discovery of a family of small polypeptides (less than 10 kD). The salient features of these cytokines are the presence of four cysteine amino acids (first two separated by one amino acid; C-X-C) and their ability to induce neutrophil chemotaxis and activation.

Expression of interleukin-1 and interleukin-1 receptor antagonist by human rheumatoid synovial tissue macrophages.

Interleukin-1 (IL-1) has protean effects in the pathogenesis of rheumatoid arthritis (RA). These effects include production of prostaglandins and collagenase from rheumatoid fibroblasts as well as upregulation of adhesion molecule expression on these cells. IL-1 can activate monocytes and neutrophils, as well as promote the growth of fibroblasts and endothelial cells.

IL-7 up-regulates the expression of IL-8 from resting and stimulated human blood monocytes.

Blood monocytes are important cellular sources of a vast array of bioactive substances, including regulatory and chemotactic cytokines. The regulation of these cytokines is of critical importance to the expression of acute and chronic inflammatory responses. IL-7, a T and B cell-activating cytokine, has recently been shown to have stimulatory effects on the expression of several monocyte-derived proinflammatory cytokines.

Anoxia-hyperoxia induces monocyte-derived interleukin-8.

Ischemia-reperfusion and hyperoxia-induced pulmonary injury are associated with the presence of activated neutrophils (PMN) and cellular injury. Although the signals orchestrating the directed migration of these PMN during the pathogenesis of these disease states remain to be fully elucidated, it appears they may be dependent upon the production of certain neutrophil activating/chemotactic factors such as C5a, leukotriene B4, platelet-activating factor, and IL-8. The production of the latter chemotaxin by mononuclear phagocytes is especially intriguing as these cells can mediate inflammatory cell migration by either directly generating IL-8, or by inducing its production from surrounding nonimmune cells.

Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis.

Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P less than 0.

Expression of interleukin-8 by lipopolysaccharide-stimulated bone marrow-derived mononuclear cells.

Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, produced by a variety of immune and nonimmune cells in response to exogenous and host-derived inflammatory stimuli. We demonstrate here that a suspension of normal bone marrow mononuclear cells, consisting principally of myeloid precursors, produces IL-8 in response to stimulation with lipopolysaccharide (LPS). IL-8-specific mRNA is rapidly induced, being detected first 30 min after stimulation.

Cytokine-induced neutrophil-derived interleukin-8.

During acute inflammation, the first line of cellular response for host defense is the neutrophil. In addition to the historic role of the neutrophil as a phagocyte, recent studies have identified this cell as an important source of a number of cytokines. In this study, we provide evidence that the neutrophil is a significant source of interleukin-8 (IL-8).

IL-1 receptor antagonist inhibits monocyte chemotactic peptide 1 generation by human mesangial cells.

The elicitation of neutrophils and monocytes from the circulation into the inflamed glomerulus is a key process in the pathogenesis of proliferative glomerulonephritis. The aim of this study was to determine the factors which regulate the expression and synthesis of the monocyte specific chemotaxin, monocyte chemotactic peptide 1 (MCP-1). Mesangial cells in culture did not constitutively express MCP-1, but could be induced to express both MCP-1 mRNA and antigenic MCP-1 by either stimulation with IL-1 alpha or TNF alpha, which are also stimuli for interleukin 8 (IL-8/NAP-1) expression and release.

Suppression of human alveolar macrophage-derived cytokines by amiloride.

Various human alveolar macrophage (AM)-derived cytokines in the lungs have been shown to be present under conditions of normal homeostasis as well as during the pathogenesis of inflammation. Although extensive investigation has demonstrated the induction of cytokines from AM, relatively little is known regarding endogenous and exogenous regulation of their production. Several pharmacologic agents, including corticosteroids, cyclooxygenase inhibitors, prostaglandins, and methyl-xanthines have been examined for their role in the modulation of mononuclear phagocyte-derived cytokines.

Neutrophilic alveolitis in idiopathic pulmonary fibrosis. The role of interleukin-8.

Idiopathic pulmonary fibrosis is an immunologically mediated pulmonary disorder in which activated alveolar macrophages (AM) and neutrophils play cardinal roles in the pathogenesis of the inflammatory lung lesion. The factors responsible for the induction and perpetuation of the neutrophilic alveolitis are not known. Recently, a novel cytokine (Interleukin-8) was described that is released by activated mononuclear phagocytes and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear leukocytes (PMN).

Expression and regulation of human alveolar macrophage-derived interleukin-1 receptor antagonist.

The alveolar macrophage (AM) is the sentinel immune cell of the distal airspace of the lung. These mononuclear phagocytic cells represent the major host defense against inhaled environmental agents. When activated, the AM has the capacity to release reactive oxygen and arachidonic acid metabolites and produce a number of cytokines, such as interleukin-1 (IL-1).

Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection.

Patients suffering from serious bacterial infection present to the hospital after early inflammatory events, such as release of tumor necrosis factor (TNF), have been initiated. The role of other cytokines, such as interleukin-8 (IL-8), a neutrophil chemoattractant and activator, in the pathophysiology of human sepsis is not well characterized, and there are only limited data on IL-6. We studied serial concentrations of TNF, IL-6 (involved in the acute-phase response), and IL-8 in plasma and leukocyte levels of mRNA for these cytokines in patients with localized and septicemic Pseudomonas pseudomallei infection on admission to the hospital and during a prolonged recovery phase (up to 30 days).

Antibodies against tumor necrosis factor prolong cardiac allograft survival in the rat.

Tumor necrosis factor (TNF)-alpha has significant biologic actions in many circumstances, such as infectious diseases, ischemia/reperfusion injury, and delayed-type hypersensitivity reactions. Based on the hypothesis that manipulation of TNF can play an important role in treatment of heart transplant rejection, the objective of this study was to determine whether anti-TNF antibodies could prolong cardiac allograft survival. Hearts from brown rats were transplanted to the necks of recipient Lewis rats.

Interleukin-6 (IL-6) gene expression and secretion by cytokine-stimulated human retinal pigment epithelial cells.

Retinal and choroidal inflammatory lesions are important causes of visual loss, but the mechanisms regulating intraocular inflammation remain poorly understood. By virtue of its position at the blood-retina barrier, the retinal pigment epithelium (RPE) cells may be critical to the initiation and propagation of ocular inflammation. Previously we showed that cytokine-stimulated RPE cells produce interleukin-8, a well-defined chemotactic factor for neutrophils and lymphocytes.

Biologic and immunohistochemical analysis of interleukin-6 expression in vivo. Constitutive and induced expression in murine polymorphonuclear and mononuclear phagocytes.

Interleukin-6 (IL-6) is considered an important multifunctional cytokine involved in the regulation of a variety of cellular responses, including the induction of acute-phase protein synthesis, lymphocyte activation, and hematopoiesis. In vitro studies have identified many cells that can produce IL-6, but the cellular sources under physiologic conditions have yet to be identified. Using immunoaffinity purified goat anti-murine IL-6, the authors performed immunohistochemical studies to localize cells expressing IL-6 in selected organs of normal and endotoxin challenged NIH-Swiss outbred mice.

Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas.

Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha.

A sensitive ELISA for the detection of human monocyte chemoattractant protein-1 (MCP-1).

The recruitment of monocytes into tissue is associated with both acute and chronic inflammation. Although monocyte migration is measured in vitro by monocyte chemotaxis, this technique is often difficult to determine the specific quantitative contribution of a monocyte chemotaxin. We have developed a sensitive sandwich ELISA for the detection of monocyte chemoattractant protein-1 (MCP-1), a highly specific monocyte activating/chemotactic peptide.

Modulation and function of intercellular adhesion molecule-1 (CD54) on human retinal pigment epithelial cells.

As part of the blood-retina barrier, the neuroectodermally-derived retinal pigment epithelial (RPE) monolayer is strategically positioned to interact with circulating leukocytes and regulate their access to the retina. We, therefore, studied whether human RPE cells express intercellular adhesion molecule-1 (ICAM-1), a specialized cell surface glycoprotein that binds the leukocyte function antigen-1 receptor present on all leukocytes. Using specific monoclonal antibody to ICAM-1, immunohistochemical staining of freshly-isolated primary and fourth passaged human RPE cells resulted in delicate reaction product that increased dramatically upon exposure to human recombinant (r) interferon-gamma (rIFN-gamma), interleukin-1-beta (rIL-1 beta), or tumor necrosis factor-alpha (rTNF-alpha).

Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone.

Mononuclear phagocytes are important immune effector cells that play a fundamental role in cellular immunity. In addition to their antigen-presenting and phagocytic activities, monocytes/macrophages produce a vast array of regulatory and chemotactic cytokines. Interleukin-8 (IL-8), a potent neutrophil-activating and chemotactic peptide, is produced in large quantities by mononuclear phagocytes and may be an important mediator of local and systemic inflammatory events.

In vitro and in vivo interleukin-8 production in human renal cortical epithelia.

The signals resulting in leukocytes infiltrating the tubulointerstitial compartment during renal inflammatory disease are not well understood. A recently described cytokine, interleukin-8 (IL-8), has been demonstrated to be chemotactic for lymphocytes and neutrophils at picomolar and nanomolar concentrations, respectively. Cytokeratin positive, renal cortical epithelial cells (RCEC) with tubular attributes were cultured from kidney tissue from six human subjects.

Interleukin-4 differentially regulates tumor necrosis factor-alpha gene expression by human T lymphocytes and monocytes.

Tumor necrosis factor-alpha (TNF-alpha), a product of both mononuclear phagocytes and T lymphocytes, is an important proximal mediator of a number of acute and chronic inflammatory disease states. In this investigation we examine the regulatory effects of the lymphocyte product interleukin-4 (IL-4) on the gene expression of TNF-alpha from stimulated human peripheral blood monocytes (PBM) and T lymphocytes. We demonstrated the dose-dependent suppression of TNF-alpha mRNA and protein synthesis from lipopolysaccharide-treated PBM by IL-4.

Interleukin-8 gene expression from human alveolar macrophages: the role of adherence.

The human alveolar macrophage (AM) is an important immune effector cell of the lung, as this cell possesses potent antimicrobial activities and has the ability to present antigen. In addition, the Am can secrete a number of regulatory and chemotactic cytokines in response to both endogenous and exogenous stimuli. In this study, we demonstrate that the adherence of AM to plastic or cellular substrates is an important activation event leading to the gene expression of novel chemotactic cytokine interleukin (IL)-8.