Serum intercellular adhesion molecule 1 variations in young children with acute otitis media.

Acute otitis media (AOM) is an inflammatory reaction in the middle ear, most often occurring in young children. Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis are the most common bacteria isolated. Intercellular adhesion molecule 1 (ICAM-1) is involved in the innate immune response to infection by microorganisms, in effective antigen presentation, and in subsequent T-cell activation. Here we prospectively studied levels of serum soluble ICAM-1 (sICAM-1) before, at the time of, and after antimicrobial treatment of AOM in a group of 138 children ages 6 to 30 months. Middle ear fluids were collected by tympanocentesis to identify otopathogens. We found that (i) serum levels of sICAM-1 were significantly higher in S. pneumoniae-, nontypeable H. influenzae-, and M. catarrhalis-infected children than in well children (P < 0.001), confirming that a systemic inflammatory response occurs during AOM; (ii) sICAM-1 levels varied from no elevation (110 ng/ml) to elevation to high levels (maximum, 1,470 ng/ml) among children with AOM; (iii) in paired samples, sICAM-1 levels increased 4- to 20-fold when children developed AOM compared to their sICAM-1 levels before infection; and (iv) the level of sICAM-1 returned to the pre-AOM level at the convalescent stage of AOM after successful antimicrobial therapy. We conclude that AOM often causes a systemic inflammatory reaction, as measured by elevation of the serum sICAM-1 level, and that a high variability in sICAM-1 responses occurs with the presence of otopathogens during AOM. Acute otitis media (AOM) is defined by the presence of middle ear effusion (MEE) with acute onset of symptoms of inflammation of the middle ear. Although more than half of patients who develop AOM have fever (14), the condition is considered a localized, mucosal infection. Currently, AOM is regarded as relatively benign due to spontaneous resolution of the infection in a majority of patients (42). The complications and sequelae of bacterial systemic invasion from the middle ear, including mastoiditis, brain abscess, and meningitis, are sufficiently rare that they have recently been considered less consequential in comparison to the consequences from the costs of antimicrobial treatment and overtreatment (2). The cause and pathogenesis of otitis media are multifactorial, involving viral and bacterial infections. The most frequently isolated bacteria in AOM are Streptococcus pneumoniae (20 to 55% of cases), nontypeable Haemophilus influenzae (15 to 40%), and Moraxella catarrhalis (10 to 25%) (12, 25, 29). When bacteria gain entry into the middle ear space, they damage the middle ear mucosa directly by releasing toxins and indirectly by provoking both specific immunological and general inflammatory responses in the host. A prominent feature of the host response is an influx of inflammatory cells into the middle ear. The migration of leukocytes into sites of inflammation is mediated by numerous factors, including intercellular adhesion molecule 1 (ICAM-1; CD54). ICAM-1 is a member of the immunoglobulin (Ig)-like superfamily (43); it is expressed on endothelial cells, monocytes, fibroblasts, leukocytes, epithelial cells, macrophages, mitogen-stimulated T lymphoblasts, germinal center B cells, and dendritic cells (48). Soluble isoforms of ICAM-1 (sICAM-1) shed from the surface of activated cells and can be quantified in biological fluids, allowing insights into early events of leukocyte recruitment (47). sICAM-1 levels have been reported to be the initial marker of inflammatory reactions in various diseases, such as allergic rhinitis, tuberculosis, sarcoidosis, rheumatoid arthritis, and meningitis (3, 7, 27, 33). However, to date, there is no information on sICAM-1 expression in children with AOM. In this study, the first to ever evaluate the concentrations of systemic (serum) sICAM-1 from children with AOM, we sought to determine if (i) the levels of sICAM-1 increased during S. pneumoniae, nontypeable H. influenzae ,o rM. catarrhalis infections; (ii) sICAM-1 levels, as a marker of the innate immune response, varied among children with AOM; (iii) sICAM-1 levels increased when children developed AOM compared to their sICAM-1 levels before infection; and (iv) the sICAM-1 level returned to the pre-AOM level at the convalescent stage of AOM after successful antimicrobial therapy.