No abstract

Low maternally derived serum immunoglobulin G (IgG) antibodies to Streptococcus pneumoniae capsular polysaccharides (PS) combined with the inability of infants to produce anti-PS antibody may explain onset of otitis media in the first 6 months of life. To explore this relation, cord blood samples were assayed for anti-PS IgG antibodies from 414 of 592 infants enrolled in a study of early onset otitis media between 1991 and 1994. Infants' ears were examined at health supervision and illness visits for the first 6 months of life in a large Minneapolis-St. Paul, Minnesota, health maintenance organization. Antibodies to seven common pneumococcal serotypes (3, 4, 6B, 14, 18C, 19F, and 23F) were measured by enzyme-linked immunoabsorbent assay (ELISA). Cox's regression analysis revealed that among infants with a sibling otitis media history, those with low concentrations of type 14 or 19F anti-PS cord blood antibody had earlier otitis media onset than those with higher cord blood antibody concentrations (relative risks (RR) (95% confidence intervals (CI)) = 1.77 (1.05-2.99) and 1.89 (1.11-3.23), respectively). Day care attendance also increased risk (RR = 1.56, 95% CI 0.96-2.52). Breastfeeding, parental smoking, and low anti-PS antibody to pneumococcal serotypes 3, 4, 6B, 18C, and 23F did not significantly affect the risk of early otitis media.

Background: CD14 promoter DNA sequence polymorphisms for the endotoxin receptor gene have been implicated in modulating allergen-specific immunoglobulin (Ig)E responses in randomly selected individuals with atopy. We sought to determine if a single nucleotide polymorphism in the CD14 promoter region is associated with atopy in atopic families, and to assess its influence on serum levels of CD14 and allergen-specific IgE and IgG1 responses. Methods: We screened 367 members of 91 Caucasian nuclear families with a history of asthma for pulmonary function by spirometry, including methacholine challenge to detect bronchial hyperreactivity, and atopy by serum total IgE and skin prick test to 14 allergens. The CD14 promoter single nucleotide polymorphism was analyzed in DNA isolated from peripheral blood mononuclear cells to identify C/C, C/T and T/T genotypes. Serum tests were done for soluble CD14 (sCD14) and dust mite-specific antibody (Der p 1-IgG1). Results: Serum sCD14 levels were not associated with clinical phenotypes (asthma, bronchial hyperreactivity or atopy). However, sCD14 levels were inversely related to both allergen-specific IgE and Der p 1-IgG1 production, but only among those with evidence of atopic sensitization. Linear regression analysis, accounting for random family effects, demonstrated a higher production of allergen-specific IgE or Der p 1-IgG1 associated with the T/T genotype and a lower level of specific IgE and IgG1 production associated with sCD14 levels. Conclusions: An element of the innate immune system (CD14) has profound effects upon modulating the acquired allergen-specific immunoglobulin responses among those with an inherited atopic predisposition.

Streptococcus pneumoniae cell wall and pneumolysin are important contributors to pneumococcal pathogenicity in some animal models. To further explore these factors in middle ear inflammation caused by pneumococci, penicillin-induced inflammatory acceleration was studied by using three closely related pneumococcal strains: a wild-type 3 strain (WT3), its pneumolysin-negative derivative (P-1), and its autolysin-negative derivative (A-1). Both middle ears of chinchillas were inoculated with one of the three pneumococcal strains. During the first 12 h, all three strains grew in vivo at the same rate, and all three strains induced similar inflammatory cell responses in middle ear fluid (MEF). Procaine penicillin G was given at 12 h to one-half of the animals in each group, and all treated chinchillas had sterile MEF at 24 h. Penicillin significantly accelerated MEF inflammatory cell influx into WT3-and P-1-infected ears at 18 and 24 h in comparison with the rate for penicillin-treated A-1-infected ears. Inflammatory cell influx was slightly, but not significantly, greater after treatment of WT3 infection than after treatment of P-1 infection. Interleukin (IL)-1␤ and IL-6, but not IL-8, concentrations in MEF at 24 h reflected the penicillin effect on MEF inflammatory cells; however, differences between treatment groups were not significant. Results suggest that pneumococcal otitis media pathogenesis is triggered principally by the inflammatory effects of intact and lytic cell wall products in the middle ear, with at most a modest additional pneumolysin effect. Investigation strategies that limit the release of these products or neutralize them warrant further investigation.

Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1␤, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-␣) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1␤, IL-6, IL-8, and TNF-␣ were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1␤ showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-␣ concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-␣ but not IL-1␤ concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae.