Promising treatment for flu-related lung injury

March 25, 2016 by Christopher Packham, Medical Xpress report
Colorized transmission electron micrograph of Avian influenza A H5N1 viruses. Credit: Public Domain

(Medical Xpress)—Influenza is highly communicable, and often causes acute lung injury and respiratory distress, particularly in aged people. Therapeutic options after infection with the virus are limited, and health organizations emphasize vaccination and sanitary measures to prevent the spread of flu viruses. Additionally, antiviral therapy does not always reduce acute lung injury, and medical researchers are keen to find new approaches.

An international group of researchers recently published the results of a study in the Proceedings of the National Academy of Sciences that treated H5N1-infected mice with multipotent mesenchymal stromal cells (MSCs), which significantly reduced the impairment of fluid clearance from the alveoli and prevented or reduced . In fact, the results of this mouse trial were so remarkable that the authors wrote, "This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation."

The H5N1 and H7N9 viruses target lung epithelial cells—this is the gas exchange interface where oxygen becomes available to the blood supply. These cells are also responsible for transporting water, sodium and chloride away from the apical surface of the alveolar epithelium; when this process is impaired, the result is acute .

Observing that MSCs have beneficial therapeutic effects for lung injuries resulting from other types of bacterial and viral illnesses, the researchers studied the effects of MSC treatment on two , H5N1 and H1N1. In the course of their study, the researchers discovered that H5N1 dysregulates alveolar fluid clearance and protein permeability by causing the down-regulation of the lung's alveolar sodium and chloride transporters.

They write, "When we cocultured alveolar epithelium with MSCs, these injury mechanisms were prevented or reduced." This led them to attempt treating mice infected with H5N1, which resulted in a "clinically significant reduction in lung pathology and increased survival in association with a modulation of these pathogenic mechanisms in vivo."

The H5N1 and other viruses induce the alveolar epithelium to produce factors that down-regulate its ability to clear fluid from the lungs; the seasonal H1N1 virus does not have this effect on the epithelium, and mice infected with H1N1 did not have the same therapeutic results. Additionally, the MSC treatment was only effective in older mice, those eight to 12 months old. Results were not significant in younger mice aged six to eight weeks.

The authors note that aged animals have lower expression of genes involved in cell activation and migration of cytokine and chemokine receptors. "Thus, younger animals have more potent endogenous MSC responses, whereas exogenous MSC therapy is more likely to exert an apparent benefit in older animals," they write.

They also note that the goal of their study was to determine the impact of MSC therapy on the progression of severe infection; they recommend that future studies examine the interactions of MSCs with antivirals, and that researchers further investigate the effects of age on MSC therapy.

Explore further: Antioxidants improve lung immune markers in HIV-infected patients who are immune non-responders

More information: Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo. PNAS 2016 ; published ahead of print March 14, 2016, DOI: 10.1073/pnas.1601911113

Abstract
Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

Related Stories

Antioxidants improve lung immune markers in HIV-infected patients who are immune non-responders

March 8, 2016
Some people with HIV infection experience a limited recovery of their T cell counts after they start antiretroviral therapy, even though the virus is well controlled. This leaves them at higher risk for other infections, ...

H5N1 virus targets pulmonary endothelial cells

January 20, 2012
The H5N1 virus has killed roughly 60 percent of humans infected, a mortality rate which is orders of magnitude higher than that of seasonal influenza virus. Many victims of the former fall heir to acute respiratory distress  ...

Fatty acids could lead to flu drug

March 7, 2013
Flu viruses are a major cause of death and sickness around the world, and antiviral drugs currently do not protect the most seriously ill patients. A study published March 7th by Cell Press in the journal Cell reveals that ...

Team discovers lung regeneration mechanism

November 12, 2014
A research team led by Jackson Laboratory Professors Frank McKeon, Ph.D., and Wa Xian, Ph.D., reports on the role of certain lung stem cells in regenerating lungs damaged by disease.

Mitophagy in macrophages is a key step toward pulmonary fibrosis

February 24, 2016
Idiopathic pulmonary fibrosis is a devastating disease, and recently approved therapies have limited efficacy. Lungs become damaged with fibrotic scarring, and the median length of survival after diagnosis is three to five ...

Study points to essential role of IL-22 in lung repair after the flu

March 11, 2013
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 ...

Recommended for you

Scientists produce human intestinal lining that re-creates living tissue inside organ-chip

February 16, 2018
Investigators have demonstrated how cells of a human intestinal lining created outside an individual's body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing ...

Researcher explains how statistics, neuroscience improve anesthesiology

February 16, 2018
It's intuitive that anesthesia operates in the brain, but the standard protocol among anesthesiologists when monitoring and dosing patients during surgery is to rely on indirect signs of arousal like movement, and changes ...

Team reports progress in pursuit of sickle cell cure

February 16, 2018
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, according to Rice University bioengineer Gang Bao.

Data wave hits health care

February 16, 2018
Technology used by Facebook, Google and Amazon to turn spoken language into text, recognize faces and target advertising could help doctors fight one of the deadliest infections in American hospitals.

Appetite-controlling molecule could prevent 'rebound' weight gain after dieting

February 15, 2018
Scientists have revealed how mice control their appetite when under stress such as cold temperatures and starvation, according to a new study by Monash University and St Vincent's Institute in Melbourne. The results shed ...

First study of radiation exposure in human gut Organ Chip device offers hope for better radioprotective drugs

February 14, 2018
Chernobyl. Three Mile Island. Fukushima. Accidents at nuclear power plants can potentially cause massive destruction and expose workers and civilians to dangerous levels of radiation that lead to cancerous genetic mutations ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.