Estrogen aggravates inflammation in PA pneumonia in CF mice
Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa).
A role for gender hormones in the causation of the CF "gender gap"has been proposed. The female gender hormone 17beta-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others.
Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules.
Recent evidence suggests a central role for the IL-23/ IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with P.aeruginosa by a Th17-mediated mechanism.
Results: Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the P. aeruginosa strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils).
Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid.
The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against P. aeruginosa in vitro.
Conclusions: Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences.
Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with P. aeruginosa in the CF lung.
Author: Yufa WangElvis CelaStephane GagnonNeil Sweezey
Credits/Source: Respiratory Research 2010, 11:166
Showing posts with label estrogen. Show all posts
Showing posts with label estrogen. Show all posts
Friday, December 3, 2010
Wednesday, August 11, 2010
Estrogen and CF women
Independent.ie
Contraceptive pill offers hope for cystic fibrosis sufferers
By Grainne Cunningham
Tuesday August 10 2010
DOCTORS are to consider treating female cystic fibrosis (CF) sufferers with the contraceptive pill in order to radically improve their health.
Newly published groundbreaking research found a clear link between an increase in levels of the female hormone oestrogen and the body's ability to fight the disease.
The Pill would allow levels of the hormone to be better regulated, thus giving the body a better chance to fight the disease.
Female sufferers of CF typically have much poorer survival rates than males with the potentially deadly condition.
Yesterday, the mother of a seven-year-old girl with CF welcomed the news as "optimistic" and said it offered reassurance to the families of sufferers that new methods of treatment would be available in the future.
Researchers at the Royal College of Surgeons in Ireland (RCSI) and Beaumont Hospital found a clear link between higher levels of oestrogen and the ability of the body to fight the disease.
Cystic fibrosis is an inherited disease that affects the lungs and the digestive system.
A build-up of mucus can make it difficult to clear bacteria and leads to cycles of lung infections, causing long-term damage and sometimes death.
The new study found that oestrogen hampers the creation of infection-fighting white blood cells in the lungs.
Ireland has the highest incidence of CF in the world, with almost four times the rate of other EU countries and the US.
During the menstrual cycle, higher levels of oestrogen increase women's risk of acquiring an infection and reduce the body's ability to fight bacteria, according to the study, which was published in the 'American Journal of Respiratory and Critical Care Medicine'.
The joint lead author, Dr Sanjay Chotirmall, said he hoped the findings would help narrow the gender gap in CF by "identifying new potential targets for treatment, such as stabilisation of oestrogen levels, or more aggressively employing preventative strategies against infection during the one week of the cycle when oestrogen levels are at their highest".
Insight
Dr Chotirmall, a specialist registrar in respiratory medicine, said the research was praised by the distinguished 'Faculty of 1000 Biology' guide for offering insight into the best way forward for treating CF.
The common Pill could prove to be a more valuable option than anti-inflammatory medicines, he suggested.
Deborah Kett, whose seven-year-old daughter Hannah has CF, said: "It's nice to get good news for a change."
She said the development would be particularly welcomed by families with girls in their teens, as they would have a new option to turn to immediately.
"When you hear something like this, it does give you hope, and that is particularly important for grandparents, siblings and others who may not be involved in the day-to-day care but are offering emotional support," Mrs Kett said.
Responding to the new research, the Cystic Fibrosis Association of Ireland welcomed the findings and commended the RCSI for its pioneering work.
"Cystic fibrosis continuous to be the most common life-threatening inherited disease in the country.
"Indeed, Ireland has the highest prevalence, and most severe types, of cystic fibrosis in the world, so we look forward to any possible future medical advances," she said.
Meanwhile, a new €1m outpatient unit for CF patients will open at Beaumont Hospital in the coming weeks.
The 580sq.m unit will consist of consultation and treatment rooms as well as a physiotherapy area and will be in addition to the six-bed in-patient centre already open at the hospital.
A spokesman for St Vincent's Hospital said discussions were still taking place with the contractor for the building of a 100-bed block which would include a CF unit comprising single-room beds.
- Grainne Cunningham
http://www.independent.ie/health/latest-news/contraceptive-pill-offers-hope-for-cystic-fibrosis-sufferers-2290598.html
Contraceptive pill offers hope for cystic fibrosis sufferers
By Grainne Cunningham
Tuesday August 10 2010
DOCTORS are to consider treating female cystic fibrosis (CF) sufferers with the contraceptive pill in order to radically improve their health.
Newly published groundbreaking research found a clear link between an increase in levels of the female hormone oestrogen and the body's ability to fight the disease.
The Pill would allow levels of the hormone to be better regulated, thus giving the body a better chance to fight the disease.
Female sufferers of CF typically have much poorer survival rates than males with the potentially deadly condition.
Yesterday, the mother of a seven-year-old girl with CF welcomed the news as "optimistic" and said it offered reassurance to the families of sufferers that new methods of treatment would be available in the future.
Researchers at the Royal College of Surgeons in Ireland (RCSI) and Beaumont Hospital found a clear link between higher levels of oestrogen and the ability of the body to fight the disease.
Cystic fibrosis is an inherited disease that affects the lungs and the digestive system.
A build-up of mucus can make it difficult to clear bacteria and leads to cycles of lung infections, causing long-term damage and sometimes death.
The new study found that oestrogen hampers the creation of infection-fighting white blood cells in the lungs.
Ireland has the highest incidence of CF in the world, with almost four times the rate of other EU countries and the US.
During the menstrual cycle, higher levels of oestrogen increase women's risk of acquiring an infection and reduce the body's ability to fight bacteria, according to the study, which was published in the 'American Journal of Respiratory and Critical Care Medicine'.
The joint lead author, Dr Sanjay Chotirmall, said he hoped the findings would help narrow the gender gap in CF by "identifying new potential targets for treatment, such as stabilisation of oestrogen levels, or more aggressively employing preventative strategies against infection during the one week of the cycle when oestrogen levels are at their highest".
Insight
Dr Chotirmall, a specialist registrar in respiratory medicine, said the research was praised by the distinguished 'Faculty of 1000 Biology' guide for offering insight into the best way forward for treating CF.
The common Pill could prove to be a more valuable option than anti-inflammatory medicines, he suggested.
Deborah Kett, whose seven-year-old daughter Hannah has CF, said: "It's nice to get good news for a change."
She said the development would be particularly welcomed by families with girls in their teens, as they would have a new option to turn to immediately.
"When you hear something like this, it does give you hope, and that is particularly important for grandparents, siblings and others who may not be involved in the day-to-day care but are offering emotional support," Mrs Kett said.
Responding to the new research, the Cystic Fibrosis Association of Ireland welcomed the findings and commended the RCSI for its pioneering work.
"Cystic fibrosis continuous to be the most common life-threatening inherited disease in the country.
"Indeed, Ireland has the highest prevalence, and most severe types, of cystic fibrosis in the world, so we look forward to any possible future medical advances," she said.
Meanwhile, a new €1m outpatient unit for CF patients will open at Beaumont Hospital in the coming weeks.
The 580sq.m unit will consist of consultation and treatment rooms as well as a physiotherapy area and will be in addition to the six-bed in-patient centre already open at the hospital.
A spokesman for St Vincent's Hospital said discussions were still taking place with the contractor for the building of a 100-bed block which would include a CF unit comprising single-room beds.
- Grainne Cunningham
http://www.independent.ie/health/latest-news/contraceptive-pill-offers-hope-for-cystic-fibrosis-sufferers-2290598.html
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