Locally produced pro-inflammatory cytokines are considered to play an important role in the initiation and/or maintenance of inflammatory diseases. In cholesteatomatous lesions there are increased levels of some cytokines and inflammatory mediators like interleukin 1, tumor necrosis factor and colony-stimulating factor, etc. Interleukin 6 (IL-6) can be produced by different cells present in cholesteatoma (e.g. keratinocytes, lymphocytes, fibroblasts and macrophages). Until now, no data have been available on the role of IL-6 in cholesteatoma. In this study we used immunohistochemistry to investigate the presence and distribution of IL-6 in tissue samples from cholesteatoma patients. Levels of the cytokine were quantified in tissue extracts using an enzyme-linked immunosorbent assay. Finally, the presence of biologically active IL-6 was analyzed in the murine cell line 7TD1. Human skin samples obtained from the external ear canal were used as controls. Using the anti-IL-6 antibody in an alkaline phosphatase anti alkaline phosphatase technique, a moderate diffuse staining of the whole epidermis was observed in sections of normal skin. In cryostat sections of cholesteatoma samples, a stronger staining of the whole epithelium was observed. Many of the cells infiltrating the cholesteatoma stroma also showed positive immunostainings. The concentration of IL-6 in relation to the total protein concentration in cholesteatoma (119.33 +/- 30) were higher than in human skin (9.16 +/- 13). While IL-6 activity was not detected in skin samples, two of the ten cholesteatoma samples studied showed a stimulatory effect when incubated with the cell line 7TD1. The overexpression of IL-6 in middle ear cholesteatoma suggests a participation of this cytokine in some of the clinical features seen: epithelial hyperproliferation and bone resorption. The absence of biological activity in the majority of the cholesteatoma samples points to the presence of natural inhibitors for IL-6.
Cytokine networks are now presumed to play an essential role in the pathogenesis of middle ear cholesteatoma. Of the factors identified in cholesteatoma, interleukin-I (IL-1)-alpha appears to be especially important because of its stimulation of keratinocyte proliferation as well induction of bone resorption. To further characterize the possible role of IL-1 in the pathogenesis of cholesteatoma, we quantified the levels of IL-1 and IL-1-receptor antagonist (IL-1-RA) present using the bicinchonic acid protein assay and enzyme-linked immunosorbent assay (ELISA) on tissue extracts from 20 cholesteatoma specimens. The presence of biologically active IL-1 was also analyzed, using the cell line LBRM-33 and an ELISA for the detection of interleukin-2 (IL-2). Human skin obtained from the external ear canal was used as control. The amounts of IL-1-alpha in cholesteatoma (34.9 +/- 19.5) were higher than in human skin (6.7 +/- 2.8). The observed differences were statistically significant by Student's t-test (P < 0.01). Skin samples showed elevated concentrations of IL-1-RA (248.3 +/- 30.2) in comparison to that in the cholesteatoma (80.8 +/- 13.5). This was also statistically significant (P < 0.01). Whereas IL-1 activity was not detected in skin samples, all cholesteatoma specimens studied showed a stimulation effect on the production of IL-2 when incubated with the cell line LBRM-33. The results point to an over-expression of IL-1 concurrent with a decreased secretion of IL-1-RA in middle ear cholesteatoma. Furthermore IL-1-RA production is deficient relative to total IL-1 production, resulting in the presence of active IL-1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.