Interleukin-8 expression in otitis media.
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).
Maxwell
K S
KS
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-3105.
Fitzgerald
J E
JE
Burleson
J A
JA
Leonard
G
G
Carpenter
R
R
Kreutzer
D L
DL
D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D016209:Interleukin-8 / Q000032:analysis* / Q000235:genetics; D008297:Male; D008876:Middle Ear Ventilation; D010034:Otitis Media with Effusion / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D011506:Proteins / Q000032:analysis / Q000235:genetics; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha