Cytokines and anti-cytokines as therapeutics — An update

Tayal, Vandana; Kalra, Bhupinder Singh

doi:10.1016/j.ejphar.2007.10.049

Cited by 169 publications

(123 citation statements)

References 76 publications

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“…This cytokine is mainly produced by keratinocytes which are stimulated by irritants. Exposure to TNF-a causes Langerhans cells to migrate to draining lymph nodes, which allows for sensitization of naïve T cells [13,16]. Evidence of overexpression of TNF-a in tissue biopsies of patients with pyoderma gangrenosum has been reported by Bister et al [20].…”

Section: Discussionmentioning

confidence: 96%

“…Important immune cells, such as dendritic cells, keratinocytes, T lymphocytes, plasma cells, monocytes/macrophages and granulocytes, and a vast array of cytokines and chemokines play a pivotal immunopathogenetic role [12][13][14][15][16]. In the case of PV it seems reasonable to speculate that lymphocyte antigen stimulation takes place in the oral mucosa with subsequent clonal proliferation in lymph nodes and recirculation to the oral mucosa with cytokine release and recruitment of neutrophils.…”

Section: Introductionmentioning

confidence: 99%

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Pyostomatitis Vegetans: Cellular Immune Profile and Expression of IL-6, IL-8 and TNF-α

Ficarra

Baroni

Massi

2009

Head and Neck Pathol

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The aim of this study was to investigate the cellular immune profile and the expression of IL-6, IL-8 and TNF-a in tissue biopsies of pyostomatitis vegetans (PV). Working hypothesis was that knowledge of the cellular immune profile and role of mediators such as IL-6, IL-8 AND TNF-alpha may contribute to a better understanding of the pathogenesis of this rare entity. Archival tissues from three patients with clinically and histologically confirmed PV were studied. Analysis of the immune profile of the cellular infiltrate and expression of IL-6 and IL-8 were evaluated by immunohistochemistry. ISH was performed to evaluate the expression of TNF-a. Biopsy tissues from erythema multiforme, recurrent aphthous stomatitis, lichen planus and normal buccal mucosa were analyzed as controls. All patients were affected by multiple mucosal ulcerations and yellow pustules mainly located in the vestibular, gingival and palatal mucosa. Histopathologically, all specimens showed ulcerated epithelium with characteristic intraepithelial and/or subepithelial microabscesses containing abundant eosinophils plus a mixed infiltrate composed of lymphocytes and neutrophils. Cellular immune profile of the inflammatory infiltrate revealed a predominance of T-lymphocytes, mainly of cytotoxic (CD3?/CD8?) phenotype, over B-cells. CD20? B-lymphocytes were also identified to a lesser degree among the lymphoid cells present in the lamina propria. Overexpression of IL-6 and TNF-a was found in both epithelial and inflammatory mononuclear cells. IL-8 expression was shown in the mononuclear cells scattered among the inflammatory infiltrate. Similar findings of overexpression of IL-6, IL-8 and TNF-a were, however, found in control tissues. In PV lesions, the inflammatory infiltrate shows a predominance of cytotoxic lymphocytes. Expression of IL-6, IL-8 and TNF-a, although not specific to PV, appears up-regulated thus these cytokines would represent a suitable therapeutic target. However, the complexity of the cytokine network and their numerous functions require further studies in order to confirm our findings.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Pyostomatitis Vegetans: Cellular Immune Profile and Expression of IL-6, IL-8 and TNF-α

Ficarra

Baroni

Massi

2009

Head and Neck Pathol

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“…IFN-a has been used with varying potency in the treatment of several malignancies (30). Recent studies show that IFNs may be a valuable tool in the supportive treatment of advanced HCC (6,31).…”

Section: Discussionmentioning

confidence: 99%

IFN-α–Induced Apoptosis in Hepatocellular Carcinoma Involves Promyelocytic Leukemia Protein and TRAIL Independently of p53

et al. 2009

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IFNs are pleiotropic cytokines that have been shown to be important regulators of cell growth. IFN-A has recently been recognized to harbor therapeutic potential in prevention and treatment of hepatocellular carcinoma (HCC). However, HCC cells respond differentially to IFN treatment, the mechanism of which is largely unknown. To address this issue, we analyzed the effect of IFN-A on different liver tumor cell lines. We found that growth inhibiting effects of IFN-A in hepatoma cells require PML-NB induction and, moreover, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on the mRNA and protein level.

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“…32 However, only very few cytokines have made their way to the clinic, mainly due to their short half-life and adverse side effects. Their plasma stability and circulation life-span can be increased through PEGylation (e.g., PEGASYS and PEGIntron), liposomal encapsulation, or coupling to carriers.…”

Section: Discussionmentioning

confidence: 99%

Novel engineered targeted interferon-gamma blocks hepatic fibrogenesis in mice

et al. 2011

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Liver fibrogenesis is a process tightly controlled by endogenous anti-and pro-fibrogenic factors. Interferon gamma (IFNc) is a potent antifibrogenic cytokine in vitro and might therefore represent a powerful therapeutic entity. However, its poor pharmacokinetics and adverse effects, due to the presence of IFNc receptors on nearly all cells, prevented its clinical application so far. We hypothesized that delivery of IFNc specifically to the disease-inducing cells and concurrently avoiding its binding to nontarget cells might increase therapeutic efficacy and avoid side effects. We conjugated IFNc to a cyclic peptide recognizing the plateletderived growth factor beta receptor (PDGFbR) which is strongly up-regulated on activated hepatic stellate cells (HSC), the key effector cells responsible for hepatic fibrogenesis. The IFNc conjugates were analyzed in vitro for PDGFbR-specific binding and biological effects and in vivo in acute (early) and chronic (progressive and established) carbon-tetrachlorideinduced liver fibrosis in mice. The targeted-IFNc construct showed PDGFbR-specific binding to fibroblasts and HSC and inhibited their activation in vitro. In vivo, the targeted-IFNc construct attenuated local HSC activation in an acute liver injury model. In the established liver fibrosis model, it not only strongly inhibited fibrogenesis but also induced fibrolysis. In contrast, nontargeted IFNc was ineffective in both models. Moreover, in contrast to unmodified IFNc, our engineered targeted-IFNc did not induce IFNc-related side effects such as systemic inflammation, hyperthermia, elevated plasma triglyceride levels, and neurotropic effects. Conclusion: This study presents a novel HSC-targeted engineered-IFNc, which in contrast to systemic IFNc, blocked liver fibrogenesis and is devoid of side effects, by specifically acting on the key pathogenic cells within the liver. (HEPATOLOGY 2011;54:586-596)

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Cytokines and anti-cytokines as therapeutics — An update

Cited by 169 publications

References 76 publications

Pyostomatitis Vegetans: Cellular Immune Profile and Expression of IL-6, IL-8 and TNF-α

Pyostomatitis Vegetans: Cellular Immune Profile and Expression of IL-6, IL-8 and TNF-α

IFN-α–Induced Apoptosis in Hepatocellular Carcinoma Involves Promyelocytic Leukemia Protein and TRAIL Independently of p53

Novel engineered targeted interferon-gamma blocks hepatic fibrogenesis in mice

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