Study points to essential role of IL-22 in lung repair after the flu
Once the initial episode of influenza has passed, the chronic effects tend to be overlooked. The results of a new study indicate that the cytokine interleukin-22 (IL-22) plays a critical role in normal lung repair following influenza infection. This study is published in the April 2013 issue of the American Journal of Pathology.
"With the increasing prevalence of more infective and/or virulent strains of influenza, understanding the impact of virus on the host epithelium and the processes involved in lung repair are of great importance," says John F. Alcorn, PhD, an immunologist affiliated with the department of pediatrics at the Children's Hospital of Pittsburgh of UPMC. He notes that the findings open up new possibilities for developing therapeutic agents that promote recovery of normal lung function and architecture after influenza infection and lessen the likelihood of secondary infections. "A key finding is that even after the resolution of infection, influenza results in lung parenchymal remodeling that may be critical to susceptibility to further injury," says Dr. Alcorn.
This series of experiments used 6- to 8-week-old wild-type (WT) mice (C57BL/6 strain) as well as IL-22–deficient mice, infected with influenza A PR/8/34 H1N1 or control vehicle. To determine the distribution of IL-22 in the lung, they used immunohistochemistry for the high affinity IL-22Ra1 receptor. Investigators found that in WT mice not inflected with influenza, IL-22 receptors were distributed on epithelial cells of the large and small airways, but not within the parenchyma. They noted that this receptor distribution suggests that in the absence of lung injury, IL-22 interacts mainly with the bronchial epithelial cells.
By 21 days post influenza infection, IL-22 receptors were observed in parenchymal tissue in injured areas, such as alveoli under repair. Researchers suggest that the IL-22 receptor can be upregulated at sites of influenza-associated injury.
The investigators also reported that 10 days after influenza infection, IL-22–deficient mice showed significantly more severe damage and greater lung edema than WT control mice, as indicated by higher lactate dehydrogenase levels and more total protein content in bronchoalveolar lavage. No differences were found in viral load. Another indication of more severe lung injury was an increase in the number of lymphocytes in the IL-22–deficient animals.
IL-22–deficient mice also showed functional impairments. For instance, those infected with influenza showed significantly decreased compliance (referring to lung distensibility) and increased hysteresis (referring to compliance differences during inspiration and expiration), indicating lung stiffness. Histological examination 21 days after influenza infection showed that IL-22–deficient mice displayed regions of diffuse inflammation and alveolar injury, few areas of metaplasia, higher intimal thickening, proteinaceous accumulation, and increased collagen deposition compared to WT mice. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes in the mice lacking IL-22.
"The role of IL-22 in promoting epithelial repair is emerging. We demonstrate that IL-22 plays a critical role in regulating pulmonary epithelial repair responses during influenza infection and resolution," says Dr. Alcorn. IL-22 is currently under development as a potential therapeutic in human clinical trials.
More information: "IL-22 is essential for lung epithelial repair following influenza infection," by Derek A. Pociask, Erich V. Scheller, Sivanarayana Mandalapu, et al. (DOI: dx.doi.org/10.1016… .2012.12.007). It appears in the American Journal of Pathology, Volume 182, Issue 4 (April 2013)
Journal reference: American Journal of Pathology
Provided by Elsevier
- Il-22 gene delivers the goods and decreases intestinal inflammation Jan 02, 2008 | not rated yet | 0
- Researcher identifies new target to prevent fatal flu lung complication Sep 29, 2009 | not rated yet | 0
- Study reveals flu-fighting role for well-known immune component Jun 26, 2012 | not rated yet | 0
- 2009 H1N1 pandemic flu more damaging to lungs, opens opportunities for bacterial infection Sep 19, 2011 | not rated yet | 0
- Transcription factor regulates protein that dampens immune responses Jun 17, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
17 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research 5 hours ago | not rated yet | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research 5 hours ago | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research 7 hours ago | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research 7 hours ago | 5 / 5 (2) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research 9 hours ago | 5 / 5 (2) | 0
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
3 hours ago | 4.7 / 5 (3) | 0 |
Teams of highly respected Alzheimer's researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.
7 hours ago | 5 / 5 (1) | 2 |
(HealthDay)—Type 2 diabetes is more aggressive in children than adults, with signs of serious complications seen just a few years after diagnosis, new research finds.
1 hour ago | not rated yet | 0
A brief visual task can predict IQ, according to a new study. This surprisingly simple exercise measures the brain's unconscious ability to filter out visual movement. The study shows that individuals whose ...
9 hours ago | 4.9 / 5 (7) | 0 |
Little is known about why asthma develops, how it constricts the airway or why response to treatments varies between patients. Now, a team of researchers at Weill Cornell Medical College, Columbia University Medical Center ...
7 hours ago | not rated yet | 0 |
Ethnic background plays a surprisingly large role in how diabetes develops on a cellular level, according to two new studies led by researchers at the Stanford University School of Medicine.
5 hours ago | not rated yet | 0 |