Interleukin-10 promoter polymorphism as risk factor to develop invasive pulmonary aspergillosis

Sainz, Juan; Hassan, Laila; Pérez, Eugenio Sanz; Romero, Antonio; Moratalla, Antonio; López-Fernández, Elisa; Oyonarte, Salvador; Jurado, Manuel

doi:10.1016/j.imlet.2007.01.005

Cited by 77 publications

(52 citation statements)

References 38 publications

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“…Immunocompetent IL-10-deficient animals were similarly resistant to infection when given intravenous conidia (43). Consistent with this, the presence of a human IL-10 promoter polymorphism resulting in reduced IL-10 expression levels in recipients of allogeneic bone marrow transplantation was associated with a reduced incidence of invasive aspergillosis (147,153). IL-6 deficiency in both immunocompetent mice and animals treated with corticosteroids resulted in greater lung fungal contents and reduced survival associated with the impaired conidiocidal activity of lung phagocytes, which was restored after the addition of recombinant IL-6 (35).…”

Section: Cytokines In Innate Leukocyte Activationsupporting

confidence: 58%

Innate Immunity toAspergillusSpecies

Park¹,

2009

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SUMMARY All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction.

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Section: Cytokines In Innate Leukocyte Activationsupporting

confidence: 58%

Innate Immunity toAspergillusSpecies

Park¹,

2009

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“…Meanwhile, significant changes in the cytokine levels of the lung homogenates were recorded among all three groups, with markedly elevated levels of both TNF-α and IL-10 at 24, 48, and 72 h with AMB plus NAC treatment. Studies of the IPA murine model have demonstrated that resistance to infection is associated with the production of Th1 cytokines, whereas Th2-cytokine release was correlated with disease progression [32,38,39] . Aihara et al previously reported that NAC could increase Th1/Th2 cytokine levels in vitro [40] .…”

Section: Discussionmentioning

confidence: 99%

NAC is associated with additional alleviation of lung injury induced by invasive pulmonary aspergillosis in a neutropenic model

Jian

et al. 2009

Acta Pharmacol Sin

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Aim: Neutropenic individuals are at high risk for invasive pulmonary aspergillosis (IPA), a life-threatening infection. To evaluate the therapeutic potential of antioxidants, IPA was induced in neutropenic mice and the effect of N-acetyl-l-cysteine (NAC) on oxidative stress levels and lung injury was analyzed. Methods: Mice were pretreated with three daily intraperitoneal injections of 150 mg/kg cyclophosphamide, followed by intratracheal inoculation with 4.5×10 6 conidia of Aspergillus fumigatus. The infected mice were then randomly assigned to an amphotericin B (AMB) group, an AMB plus NAC group, or an untreated control (C) group. In each group, the duration of treatment was 24, 48, or 72 h, and activities such as appearance, feeding, and dermal temperature were observed throughout the experiment. Sera and lung tissues were collected and analyzed by quantitative enzyme-linked immunosorbent assay (ELISA) for total protein, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) levels. The wet/dry weight ratio of the lung was also calculated and lung sections were stained with hematoxylin-eosin for pathological examination and with methenamine silver stain for fungus detection. Results: Compared with the mice untreated with NAC, mice in the AMB plus NAC group had increased SOD and reduced MDA levels both systemically and locally at 24, 48, and 72 h after inoculation with conidia. NAC treatment also decreased the pulmonary protein content at 48 and 72 h and the lung wet/dry weight ratio at 24 and 48 h. Additionally, NAC enhanced pulmonary production of TNF-α and IL-10 at 24 h and 48 h. Conclusion: In combination with antifungal therapy, NAC treatment can alleviate oxidative stress and lung injury associated with IPA in neutropenic mice.

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“…Three major single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene (Ϫ1082 G/A, Ϫ819 C/T, and Ϫ592 C/A) determine the level of production of IL-10; the resulting GCC allele has been associated with high IL-10 production, whereas the ATA allele has been associated with low IL-10 production. Polymorphisms in the IL-10 gene have been shown to affect the risk for septic shock and its outcomes (21), the incidence of invasive aspergillosis (20), the progression of hepatitis B (6), and paracoccidioidomycosis (4), among other infections.…”

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confidence: 99%

Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-ProducingEscherichia coliin Travelers from the United States Who Are Visiting Mexico

Flores

DuPont

Lee

et al. 2008

Clin Vaccine Immunol

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Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenicEscherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position ؊1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position ؊819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position ؊592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.Traveler's diarrhea (TD) affects up to 60% of short-term U.S. visitors to developing countries (23). Although TD is a self-limited disease with few acute complications, it can result in significant transient discomfort, cause changes in travel plans, and produce temporary incapacitation (25). TD has also been associated with long-term complications, such as postinfectious reactive arthritis, (27) Guillain-Barré neuropathy (22), and postinfectious irritable bowel syndrome (17).Up to 85% of TD cases are bacterial in origin. In Mexico, enterotoxigenic Escherichia coli (ETEC) is the single mostcommonly identified agent in the stools of travelers with diarrhea, ranging from 19% to 40% of cases (3). ETEC isolates from travelers can produce heat-labile toxin (LT), heat-stable toxin (ST), or both toxins simultaneously (LT/ST). Approximately 43% to 68% of strains isolated from subjects with TD in Mexico produce LT alone or in combination with ST (1,11,13). Contact with ETEC LT, as a result of vaccination or after natural infection, is associated with the production of LTspecific antibodies (8, 15) and may serve as an indicator of ETEC LT exposure.Previous studies carried out in Bangladesh have demonstrated that after adjusting for confounding variables, such as age and prior exposure, ETEC LT can be identified with similar frequencies in the stools of children with diarrhea and healthy controls (...

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Interleukin-10 promoter polymorphism as risk factor to develop invasive pulmonary aspergillosis

Cited by 77 publications

References 38 publications

Innate Immunity toAspergillusSpecies

Innate Immunity toAspergillusSpecies

NAC is associated with additional alleviation of lung injury induced by invasive pulmonary aspergillosis in a neutropenic model

Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-ProducingEscherichia coliin Travelers from the United States Who Are Visiting Mexico

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