Invertebrates do not display the level of sophistication in immune reactivity characteristic of mammals and other ‘higher’ vertebrates. Their great number and diversity of forms, however, reflect their evolutionary success and hence they must have effective mechanisms of defence to deal with parasites and pathogens and altered self tissues. Inflammation appears to be an important first line defence in all invertebrates and vertebrates. This brief review deals with the inflammatory responses of invertebrates and fish concentrating on the cell types involved and the mediators of inflammation, in particular, eicosanoids, cytokines and adhesion molecules.

Andrew F. Rowley

The evolution of inflammatory mediators

Freek J. Zijlstra

Editorial

Background: Interleukin-6 (IL-6), a pluripotent cytokine, has traditionally been considered the product of proinflammatory cells. However, many other cell types have been shown to produce IL-6. Since intestinal inflammation is commonly associated with a vigorous systemic inflammatory response, we hypothesized that intestinal epithelial and smooth muscle cells might contribute to that response by producing IL-6. We therefore studied the capacity of differentiated human intestinal epithelial and smooth muscle cell lines to produce IL-6 in response to various proinflammatory stimuli.Materials and methods: CCL-241, a human intestinal epithelial cell line, and HISM, a human intestinal muscle cell line, were grown to confluency and then treated for 24 h with various concentrations of lipopolysaccharide,Clostridium difficile culture extract containing both toxin A and toxin B, recombinant human tumor necrosis factor-alpha (TNF-α), or recombinant human interleukin-1 beta (IL-1β). Supernatants were then collected for IL-6 determination using an enzyme-linked immunosorbent assay. Cell numbers were determined using a Coulter counter. For comparison, parallel studies were performed using phorbol ester-primed U-937 and THP-1 human macrophage cell lines.Results: Both human intestinal epithelial and smooth muscle cells produced IL-6 under basal conditions. In HISM cells, but not in CCL-241 cells, IL-6 release was increased slightly by treatment with C. difficile culture extract containing both toxin A and toxin B and with lipopolysaccharide. In both cell lines, IL-6 production was profoundly stimulated by treatment with IL-1β and less so with TNF-α. Combinations of high-dose TNF-α and IL-1β may have a slightly additive, but not synergistic, effect on IL-6 release. The amount of IL-6 produced by IL-1-stimulated intestinal cell lines was 70-fold higher than that produced by stimulated macrophage cell lines.Conclusions: Both intestinal epithelial and smooth muscle cells demonstrate the ability to release significant amounts of IL-6. The profound response to IL-1β and TNF-α stimulation by both cell lines suggests that human intestinal parenchymal cells, influenced by paracrine mediators liberated from proinflammatory cells, might significantly contribute to the overall systemic inflammatory response by producing IL-6.

Edmond K. Ng

Ninder Panesar

Walter E. Longo

Marc J. Shapiro

Donald L. Kaminski

Kym C. Tolman

John E. Mazuski

Human intestinal epithelial and smooth muscle cells are potent producers of IL-6

A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC) activation and interleukin-2 receptor (IL-2R) expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R) is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting findings are discussed in the light of the data showing that sIL-2R production correlates with IL-2 production.

Calogero  Caruso

Giuseppina  Candore

Diego  Cigna

Antonio Tobia Colucci

Maria Assunta Modica

Biological significance of soluble IL-2 receptor

Cytokines play an important role in the development and persistence
of the inflammatory lesions seen in Crohn's disease and ulcerative
colitis. This review discusses the current thinking of the role of
cytokines in chronic intestinal inflammation including the
involvement of immunoregulatory cytokines within the Th1 and Th2
subsets.

G.  Radford-Smith

D. P. Jewell

The Role of Cytokines in Inflammatory Bowel Disease

Iv&#xE1;n L. Bonta

Mediators of Inflammation well on track to connect Molecular Pharmacology and Therapeutics

Ozone is an intrinsically toxic gas and its hazardous employment has led to a poor consideration of ozone therapy. The aim of this review is to indicate that a wrong dogma and several misconceptions thwart progress: in reality, properly performed ozone therapy, carried out by expert physicians, can be very useful when orthodox medicine appears inadequate. The unbelievable versatility of ozone therapy is due to the cascade of ozone-derived compounds able to act on several targets leading to a multifactorial correction of a pathological state. During the past decade, contrary to all expectations, it has been demonstrated that the judicious application of ozone in chronic infectious diseases, vasculopathies, orthopedics and even dentistry has yielded such striking results that it is deplorable that the medical establishment continues to ignore ozone therapy.

Velio Bocci

Ozone as Janus: this controversial gas can be either toxic or medically useful

Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates.

K. E. Matthys

H. Bult

Nitric oxide function in atherosclerosis

Exciting Developments for 2005

Iván L. Bonta

No speed limit now for publication of research in Mediators of Inflammation

About this journal

Mediators of Inflammation publishes papers on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules

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Chief Editor, Professor Agrawal, is an Assistant Clinical Professor of the Division of Basic and Clinical Immunology. Dr. Agrawal's research focuses on the dendritic cells of the immune system in the context of aging and autoimmunity.

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We currently have a number of Special Issues open for submission. Special Issues highlight emerging areas of research within a field, or provide a venue for a deeper investigation into an existing research area.

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Mediators of Inflammation - Table of contents

title

Mediators of Inflammation publishes papers on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules

Mediators of Inflammation