RGD Reference Report - Cytokine profiling of pulmonary aspergillosis. - Rat Genome Database

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Cytokine profiling of pulmonary aspergillosis.

Authors: Sambatakou, H  Pravica, V  Hutchinson, IV  Denning, DW 
Citation: Sambatakou H, etal., Int J Immunogenet. 2006 Aug;33(4):297-302.
RGD ID: 4981337
Pubmed: (View Article at PubMed) PMID:16893395
DOI: Full-text: DOI:10.1111/j.1744-313X.2006.00616.x

Aspergillus fumigatus is ubiquitous and yet causes invasive, chronic and allergic disease of the lung. Chronic cavitary pulmonary aspergillosis (CCPA) is a slowly destructive form of pulmonary aspergillosis, without immunocompromise. We hypothesized that CCPA cytokine gene polymorphisms would differ from patients with allergic bronchopulmonary aspergillosis (ABPA) and uninfected controls. We have profiled functional cytokine gene polymorphisms for interleukin (IL)-10, IL-15, transforming growth factors (TGF)-beta1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in patients with CCPA (n = 24) who were compared with other forms of aspergillosis (mostly ABPA) (n = 15) and with ethnically matched controls (n = 65-330). Results are described with reference to the high-producing genotype in each case. Susceptibility to aspergillosis (all patients compared with normal controls) was associated with higher frequency of the IL-15 +13689*A allele (OR = 2.37, P = 0.0028) and A/A genotype (chi(2) = 10.31, P < 0.001), with a lower frequency of the TNF-alpha-308*A/A genotype (chi(2) = 11.05, P < 0.01). Within the aspergillosis patients, CCPA is associated with lower frequency of the IL-10 -1082*G allele (OR = 0.38, P = 0.0006) and G/G genotype (chi(2) = 22.45, P < 0.001) and with a lower frequency of the TGF-beta1 +869 *T allele (OR +0.42, P < 0.0029) and T/T genotype (chi(2) = 17.82, P < 0.001) compared with non-CCPA patients and normal controls. Patients infected with Aspergillus appear to be higher producers of IL-15, a Th2-promoting cytokine, and lower producers of TNF-alpha, a cytokine central in protective responses. CCPA occurs in patients who are genetically lower producers of both IL-10 and TGF-beta1. As these cytokines are regulatory and anti-inflammatory, CCPA may be a consequence of poor inflammatory response control in the lung.

Annotation

Disease Annotations    
aspergillosis  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Il15  (interleukin 15)

Genes (Mus musculus)
Il15  (interleukin 15)

Genes (Homo sapiens)
IL15  (interleukin 15)


Additional Information