Interleukin‐8 expression in otitis media

Abstract

Based on recent studies in the authors' laboratory on the correlation of cytokines and inflammation in otitis media (OM), the authors hypothesized that in chronic otitis media with effusion (COME) interleukin-8 (IL-8) is responsible for 1. the accumulation of leukocytes in the middle ear cleft and 2. in situ leukocyte activation with subsequent tissue damage. Additionally, the authors hypothesized that IL-8 expression is at least in part under the control of interleukin-1 (IL-1) and tumor necrosis factor (TNF). To begin to test this hypothesis, middle ear effusions (MEE) obtained from children ages 2 to 90 months (mean age, 29 months) undergoing tympanostomy tube placement for the presence of these inflammatory cytokines were analyzed. For these studies, IL-8, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF-beta) were measured in MEE by radioimmunoassay (RIA) or enzyme-linked immunoassay (ELISA). IL-8, IL-1 beta, TNF-alpha, and TNF-beta were present in 92%, 67%, 77%, and 0% of effusions, respectively. The mean (+/- SEM) values for IL-8, IL-1 beta, and TNF-alpha were 4805 (+/- 913) pg/mg, 4076 (+/- 1510) pg/mg, and 163 (+/- 90) pg/mg. Further analysis indicated that levels of IL-8 correlated with IL-1 beta (R2 = .500, P = .000) and TNF-alpha (R2 = .387, P = .023). Thus the authors' studies clearly demonstrate that IL-8 is consistently present in the MEE of children with COME and is strongly correlated with levels of IL-1 beta and TNF-alpha, both known inducers of IL-8 production. These results support the authors' hypothesis that IL-1 beta, TNF-alpha, and IL-8 are intimately involved in the inflammatory cascade in the middle ear and suggest regulation of these cytokines as possible sites of future therapeutic intervention in otitis media with effusion (OME).

Cytokine regulation of mucin secretion in a human middle ear epithelial model

“…These mucins vary in size and can be membrane bound or secreted. The process of defining the specific functions of each of these mucin products in the middle ear is still ongoing.There is currently a growing body of evidence demonstrating that a cytokine mediated inflammatory response is important in the pathophysiology of acute and chronic otitis media [8][9][10][11][12][13][14][15]. This study, along with similar studies conducted in our laboratory using chinchilla middle ear epithelial cells, shows clear evidence of this cytokine mediated inflammatory response particularly as it relates to mucin pathophysiology and regulation.…”

“…Several cytokines have been found in a high percentage of these effusions, including TNF-α and IL -1β [6]. In addition to the general inflammatory regulatory mechanisms associated with these cytokines evidence exists that TNF-α and IL-1β are also integral in the inflammatory response in otitis media and regulate mucin production and secretion from middle ear epithelium [7][8][9][10][11]. Previous investigations in our laboratory using primary culture chinchilla middle ear epithelial (CMEE) cells have laid the ground work for the current investigations [12].…”

Up-Regulation of Interleukin-8 by Novel Small Cytoplasmic Molecules of NontypeableHaemophilus influenzaevia p38 and Extracellular Signal-Regulated Kinase Pathways

“…However, uncontrolled inflammation due to overproduction of proinflammatory cytokines and chemokines can cause indirect host-mediated tissue damage. Emerging studies revealed that higher-than-normal levels of IL-8 were detected in most middle ear effusions of OM (17,23) and sputum of COPD (27), suggesting that IL-8 contributes to this pathology. This is further supported by an animal model in which direct injection of IL-8 into the murine middle ear induced leukocyte accumulation at that site (13).…”

Otitis media with effusion: disease or defense?

“…Histology shows fewer mucus-secreting cells in the middle ear mucosa in serous compared to viscous OME [10]. Mucus contains water, cells, cell debris, high molecular weight compounds (mucins, proteins, and lipids), immunoglobulins, lysozyme, lactoferrin and complement components, antimicrobial peptides, leukotrienes and cytokines [3,10,[28][29][30][31][32]. These chemical defenses ensure that an antimicrobial milieu is constantly present [3].…”