Cytokines in nasopharyngeal secretions; evidence for defective IL-1β production in children with recurrent episodes of acute otitis media

Abstract

SUMMARYThe host-parasite relationship in the nasopharynx of young children with bacterial colonization and antigen uptake in the mucosa and lymphatic tissue provides an opportunity to investigate infectious inflammatory processes and responses. IL-l/:i, IL-6 and tumour necrosis factor-alpha (TNF-rt) were analysed in nasopharyngeal secretions and serum from children with or without recurrent episodes of acute otitis media, from healthy adults and adults with hypogammaglobulinaemia or selective deficiency of IgG3. Nasopharyngeal secretions generally contained substantial amounts of \L-\ii, IL-6 and TNF-a. In contrast. IL-1/'^. IL-6 and TNF-fv were not detectable in sera on the same occasion. Children were found to have higher levels of IL-1/3, IL-6 and TNF-rk than healthy adults and than adults with immunodeficiency. High levelsof IL-IJ were associated with low or undetectable levels of IL-6 and TNF-a, whereas the opposite pattern was seen in association with low levels of IL-l/l This was especially true for children with recurrent episodes of acute otitis media (RAOM). In children with nasopharyngeal colonization with Haemophilus infiuenzae, significantly higher levels of IL-1/3, IL-6 and TNF-o (P =00001. respectively) were found compared with non-colonized children. Notably, the RAOM children exhibited significantly lower levels of IL-I/i IL-6, and TNF-n in nasopharyngeal secretions {P = 0 0001, 0.01 and 0.0001, respectively) than healthy children. These results demonstrate local production of inflammatory cytokines in nasopharynx, related to bacterial colonization, and suggest that children with RAOM are poor nasopharyngeal cytokine producers.Keywords \L-\fl IL-6 tumour necrosis factor alpha nasopharyngeal secretions children INTRODLCTIONThe human nasopharynx plays a crucial role for development of immune responses to foreign microorganisms [1], and is a natural reservoir for several bacterial species, including Streptococcus pneumoniae, Haemophilus infiuenzae. the majority of which are non-typable [2]. and Moraxella (Branhamella) catarrhalis.Bacterial adherence to the mucosa is a well known phenomenon in children. Carriership of pneumococci has been monitored in several epidemiological studies, particularly in the age group 1 -2 years [3], where the colonization rate is about 90%. There is a subsequent decline in preschool children, and the colonization rate in adults is 10%. The epidemiology of nontypable H. infiuenzae is less well known, because of earlier difliculties in classifying this species. In one recent study the colonization rate was 35% in preschool children [4]. A decline with increasing age has also been demonstrated. Carriership is a Correspondence: Dr K. Lindberg. Department of Otorhinolaryngology. B5

In Vivo Adaptation and Persistence of Neisseria meningitidis within the Nasopharyngeal Mucosa

“…3). While we are unaware of similar studies being performed in humans, these elevated cytokine responses reflect that seen in the nasal washes of children with Haemophilus influenzae [27], which is presumed to colonize a similar niche within the human nasopharynx. In the CEACAM1 -humanized mice, heat-inactivated Nme caused an inflammatory response similar to that of the viable wild-type strain, whereas the cytokine response to viable but Opa-deficient meningococci was significantly lower; in the case of TNFα and IL-1β, the response to Opa-deficient meningococci was indistinguishable from the uninfected mice.…”

Nasopharyngeal Acute Phase Cytokines in Viral Upper Respiratory Infection

“…IL-1β can act through increasing the expression of IL-6 and several other cytokines (12). The acute phase cytokines may also play a beneficial role in the pathogenesis of AOM as well; Lindberg et al showed that the NPS concentrations of IL-1β, IL-6 and TNF-α were significantly lower in children with history of recurrent AOM (13), suggesting that a robust cytokine response may enhance immune responses that protect against recurrent episodes of AOM. However, these investigators did not evaluate the NPS cytokine levels during episodes of viral URI or AOM.…”

Genetic Polymorphisms in Immunoresponse GenesTNFA,IL6,IL10, andTLR4Are Associated With Recurrent Acute Otitis Media

“…9 TNF-␣ stimulates Ig and mucin production, and low TNF-␣ concentrations may compromise these defense mechanisms. 7 The association between various TNFA polymorphisms and otitis media parameters found in our study may indicate that, indeed, there is a role for these polymorphisms in TNF-␣ production in vivo.…”

“…[5][6][7][8] Remarkably, IL-1␤, IL-6, and TNF-␣ levels in nasopharyngeal secretions were found to be lower in children with recurrent otitis media than in healthy children. 9 The influence of genetically determined variations on otitis media can be illustrated by twin studies, which have shown a heritability of 57% for acute ear infections and 72% for chronic ear infections. [10][11][12][13][14] Correlation for recurrent otitis media is higher in monozygotic twins (65%-71%) compared with dizygotic twins (25%-34%).…”