Influence of Interleukin‐10 onAspergillus fumigatusInfection in Patients with Cystic Fibrosis

Abstract

Recent evidence suggests that genetic polymorphisms that affect the production of interleukin (IL)-10 may play a role in the response to pathogens in cystic fibrosis (CF). The present study was designed to investigate a possible association between alleles carried at position -1082 in the promoter region of the IL-10 gene and clinical data on 378 patients with CF. After adjustment for potential confounding variables, a significant relationship was found between the -1082GG genotype and both colonization with Aspergillus fumigatus and allergic bronchopulmonary aspergillosis. In addition, higher serum levels of IL-10 were observed in patients colonized with A. fumigatus. These results suggest that polymorphisms in the promoter region of the IL-10 gene may influence the host response to A. fumigatus in the context of CF.

Association of interleukin-10 gene haplotypes with Pseudomonas aeruginosa airway colonization in cystic fibrosis

“…We found that the percentage of colonized patients was higher among homozygous for GG at -1082 compared to subjects carrying the -1082AA genotype, and that the high-IL-10-producing haplotype GCC was associated with a greater risk of P. aeruginosa airway colonization (Table 4). This seems to be consistent with the results of Brouard et al [19], who showed a significant relationship between the -1082GG genotype and colonization with Aspergillus fumigatus in CF patients. Furthermore, other association studies of IL-10 gene polymorphisms with infectious lung diseases have shown a correlation between the same -1082GG genotype and the severity of community-acquired pneumonia and pneumococcal infection in hospitalized patients [20,21].…”

The pros and cons of immunomodulatory IL-10 gene therapy with recombinant AAV in a Cftr−/−-dependent allergy mouse model

“…This is particularly of concern as certain studies have revealed possible associations between alleles in the IL-10 promoter region responsible for higher IL-10 secretion and A. fumigatus colonization of lung. 65 These potential toxicities indicate that caution must be exercised in considering clinical applications of the potent immunomodulatory effects of rAAV1-IL-10, which might otherwise be therapeutic in a number of human diseases.…”

Diagnosis and treatment of allergic bronchopulmonary aspergillosis

“…Specifi c genetic factors have been implicated in the development of this entity. IL-10 overproduction, as conferred by the -1082GG genotype in the promoter region of the IL10 gene, signifi cantly increases the risk of colonization with A. fumigatus and the development of ABPA [9]. Further genotype analyses of patients with ABPA revealed a strong association with HLA-DR2 and HLA-DR5 alleles, whereas the HLA-DQ2 allele appears to protect against the disorder [10].…”