Cytolytic complement activity in otitis media with effusion.

Otitis media with effusion (OME) is a chronic inflammation persisting in the middle ear cavity of at least 8 weeks duration. Middle ear effusion (MEE; n = 38), samples from children suffering from OME were investigated for their direct cytolytic activity or an ability to enhance complement lysis of unsensitized bystander cells. Thirteen of the 38 MEEs had direct endogenous haemolytic activity and 27 samples had an ability to enhance serum-initiated lysis. Using an enzyme immunoassay, high levels of terminal complement complexes (TCC) were detected in the MEE samples (mean 34.1 microg/ml, range 5--89 microg/ml). This indicated strong local complement activation that had progressed to the terminal stage. As one potential factor promoting complement activation we identified both monomeric and trimeric properdin in MEE by Western blotting. By stabilizing C3 and C5 convertases properdin accelerates the alternative and terminal pathways of complement. On the other hand, the membrane attack complex (MAC) inhibitor CD59, which was found to be extensively shed into the MEE in a functionally active form, may control excessive cytotoxicity of the MEE. In conclusion, intense complement activation, up to the terminal level, maintains ongoing inflammation in the middle ear cavity and can pose a threat to the local epithelium.

Complement-regulator factor H and related proteins in otitis media with effusion.

Otitis media with effusion (OME) is a common disease in childhood. It is characterized by chronic inflammation in which the proinflammatory activity of the complement (C) system is one of the underlying factors. The C system becomes strongly activated in the middle ear effusion (MEE) fluid, but the reasons for this are not known. Here we demonstrate by using complement Bb fragment ELISA that MEE specimens strongly activate the alternative C pathway (AP) in normal human serum (NHS). Some of the MEEs were also found to promote lysis of rabbit erythrocytes by NHS. These findings indicated a disturbance in the fluid-phase regulation of the AP in MEE. The main regulator of the AP, factor H (FH), and proteins structurally related to it (FHL-1, FHR-1, -2, -3, and -4) were present in the MEE fluids of OME patients. Relative to serum, the FHR proteins were more abundant in the MEEs. In addition, we detected the recently discovered 65-kDa FH-related protein FHR-5 in the MEE. The FHR proteins share binding sites with FH in the C3d region of C3b. Thus they may compete with FH in binding to C3b and interfere with the regulatory activity of FH. Consequently, a disturbance in AP control in the MEE may lead to an ongoing excessive C activation and inflammation in OME.

Complement C3 cleavage and cytokines interleukin-1beta and tumor necrosis factor-alpha in otitis media with effusion.

OBJECTIVES: To analyze whether complement C3a anaphylatoxin, other C3 fragments, interleukin-1beta (IL-1beta), or tumor necrosis factor-alpha (TNF-alpha) contributes to inflammation in chronic otitis media with effusion (OME). METHODS: The amount of C3a was measured by enzyme-linked immunoassay. Further breakdown of C3 was analyzed by Western blotting. IL-1beta and TNF-alpha concentrations were measured by radioimmunoassay. Bacteria were analyzed by culture and polymerase chain reaction. RESULTS: Highly elevated levels of C3a and other C3 cleavage fragments were found in all middle ear effusion (MEE) samples. The mean values (+/- SEM, n = 26) for C3a, IL-1beta, and TNF-alpha were 5,973 +/- 1,124 ng/mL, 1,043 +/- 490 pg/mL, and 79 +/- 14.3 pg/mL, respectively. Comparison to an average C3 level of 555 (+/-108) microg/mL indicated that at least 40.5% +/- 6% of total C3 had become activated within the MEE. C3a concentrations were higher in the group in which the effusion had been present in the middle ear for a prolonged period (> or =4 mo) (P = .04). Children with multiple tube insertions had higher C3 (P = .006) and TNF-alpha (P = .04) concentrations in their MEE samples than those receiving their first tubes. C3 and C3a concentrations in MEE correlated to each other (correlation coefficient [r] = 0.513, P = .0056), as did concentrations of IL-1beta and TNF-alpha (r = 0.7016, P < .0001). No significant correlation was found between complement C3 or C3a levels and IL-1beta, TNF-alpha, or bacterial growth. CONCLUSIONS: Highly elevated levels of C3a in MEE indicate ongoing complement activation, which is stronger than in almost any other disease demonstrated previously. Elevated C3a levels contribute to chemotactic and inflammatory potential in the MEE and correlate with the chronicity of the disease.

Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion.

The aetiopathogenesis of chronic otitis media with effusion (OME) in children is not yet fully understood. OME is characterized by metaplasia of the epithelium and accumulation of sticky, glue-like effusion in the middle ear containing different mediators of inflammation, including activation fragments of the complement system. Here we examined whether the fluid phase complement activation is reflected in the middle ear mucosa and how the mucosa is protected against the cytolytic activity of complement. Mucosal biopsies from 18 middle ears of children with a history of chronic OME were taken. The biopsies were analysed by immunofluorescence microscopy after staining for complement fragments iC3b/C3c, C3d and C9, and regulators membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and protectin (CD59). There was a strong staining for iC3b/C3c, and a weaker one for C3d and C9 on the surface of the middle ear epithelial cells of OME patients but not in controls without OME. MCP was expressed on the hyperplastic three to four outer cell layers of the epithelium, while CD59 was expressed throughout the middle ear mucosa. The results suggest a strong ongoing complement activation and consequent inflammation in the middle ear cavity. Unrestricted complement damage of the epithelial lining is prevented by the strong expression of MCP and CD59.

Oral prednisolone is an effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes.

OBJECTIVE: To determine the efficacy of a short course of oral prednisolone as an adjuvant therapy for acute otitis media draining through tympanostomy tubes. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, children with acute discharge (<48 hours) through tympanostomy tubes received either prednisolone (2 mg/kg/d; n = 23) or placebo (n = 27) for 3 days. All children received amoxicillin/clavulanate (40/10 mg/kg/d) for 7 days. The children were examined daily at the study clinic until the drainage ceased. RESULTS: The median duration of otorrhea in the prednisolone group was 1.0 days (25% to 75% range, 1.0 to 2.0 days), compared with 3.0 days (25% to 75% range, 2.0 to 4.0 days) in the children receiving placebo (P <.001). The duration of otorrhea was

Endoscopic sinus surgery or Caldwell-Luc operation in the treatment of chronic and recurrent maxillary sinusitis.

The treatment of chronic and recurrent maxillary sinusitis has been changed in recent years. The radical Caldwell-Luc approach has increasingly been replaced by more conservative functional endoscopic sinus surgery (FESS). In the central hospital of Central Finland between 1991 and 1992, 260 patients (424 sinuses) suffering from chronic or recurrent maxillary sinusitis were operated on. Patients were classed into three groups according to the patient history of sinusitis. The plain sinus films (occipitomental projections) were evaluated. Complication rate and the need for reoperations were evaluated retrospectively after a mean follow-up time of 3.8 years. Patients in the Caldwell-Luc group had more serious disease than in the FESS or antrostomy group. The plain sinus films taken preoperatively showed more opacification in maxillary sinuses in the Caldwell-Luc group than in the FESS or antrostomy group. Complication rate was 4.4% in the Caldwell-Luc group and 2.6% in the FESS group. No serious complications existed in the whole material. Patients treated with Caldwell-Luc operation in 1991 and 1992 needed reoperation in 7/96 cases (7.3%) and 3/63 cases (4.8%), respectively. In the FESS group, patients operated 1991 and 1992 needed reoperation in 3/11 cases (27%) and 13/72 cases (18%), respectively.