Friday, April 22, 2011

GM-CSF: An Innate Ability To Fight Flu


# 5513




While just about everyone is familiar with vaccines and antivirals as preventatives or treatment for influenza, both have serious limitations.  


  • Vaccines take months to develop and manufacture, must be well matched to the circulating virus, administered weeks in advance, and have a variable effectiveness rate.


  • Antivirals often have a limited impact on the severity of illness and flu strains can over time develop resistance to them.

Today news about a new approach, that while years away from practical use, might one day help stimulate the body’s innate immune system into fighting the flu.


It’s called GM-CSF (granulocyte macrophage-colony stimulating factor), and according to a recent article in American Journal of Respiratory and Critical Care Medicine - in experiments performed on mice - it produced a remarkably effective immune response against influenza.


Specifically, it boosted levels of alveolar macrophages (AM) in the lungs.  Alveolar macrophages are part of the body’s innate immune system that seek out and destroy respiratory microbes.


A macrophage of a mouse forming two processes to phagocytize two smaller particles, possibly pathogens. – Wikipedia Commons



All of us are born with what is called an Innate Immune System that can detect, and launch a generic defense against, a wide variety of invading pathogens.


And if you think about it, were it not for this built-in immunity, none of us would survive past the first few hours or days of life.  We'd be quickly overrun by opportunistic infections.


This innate immune system also buys us time for our Adaptive Immune System to learn to recognize and fight specific pathogens. This adaptive immune system produces pathogen-specific antibodies that can remember previous encounters with a virus, and gives us acquired immunity.


Using three types of mice (wild-type, transgenic mice that do not express any GM-CSF, and transgenic mice that express GM-CSF only in the lungs), researchers inoculated them with three different influenza strains.


  • Untreated Wild-type mice, and those that were genetically unable to express any GM-CSF, all died.  

  • Mice that were genetically designed to express GM-CSF in the lungs, and Wild-Type mice treated with GM-CSF prior to infection all survived.


The major finding here is that the expression of GM-CSF in the lungs of mice provided extraordinary protection against lethal doses of several influenza virus strains.


Research further showed that it was the boost in alveolar macrophages, not T-cells or B-cells, that conveyed this protection.


While this could someday lead to a practical treatment for influenza in humans, for now this is mostly an important advance in our understanding of the way influenza works in the lungs and the workings of the innate immune system (in mice, anyway).


The standard caveats about mouse physiology vs. human physiology apply, and of course tinkering with something as complex (and incompletely understood) as the human immune system must be done cautiously.


But from a pure research standpoint, this is fascinating stuff.


First a link to the study, then some excerpts from the press release, and then I’ll be back with a little more.


Am. J. Respir. Crit. Care Med. 2011, doi:10.1164/rccm.201012-2036OC

GM-CSF in the Lung Protects Against Lethal Influenza Infection

Fang-Fang Huang, Peter F Barnes, Yan Feng, Ruben Donis, Zissis C Chroneos, Steven Idell, Timothy Allen, Daniel R Perez, Jeffrey A Whitsett, Kyri Dunussi-Joannopoulos, and Homayoun Shams

Conclusions: Granulocyte-macrophage colony stimulating factor confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.



The following is a press release from the American Thoracic Society.


New approach to defeating flu shows promise

New research on mice has shown that pulmonary administration of granulocyte macrophage-colony stimulating factor (GM-CSF) significantly reduces flu symptoms and prevents death after a lethal dose influenza virus. While GM-SCF therapy for humans as a flu prophylaxis or treatment may be years away, the study results were striking: All of the mice treated with GM-SCF survived after being infected with the influenza virus, whereas untreated mice all died from the same infection.


"Such unique and unambiguous results demonstrate the great potential of GM-CSF and may be the remedy for a critical public health priority: developing strategies to reduce the morbidity and mortality from influenza," said Homayoun Shams, PhD, principal investigator of the study.

(Continue . . . )


GM-CSF is a type of cytokine.


Cytokines, broadly speaking, are a category of signaling molecules that are used extensively for cellular communication.


They are often released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.


In this case, GM-CSF stimulates the immune system to produce granulocytes – white blood cells (neutrophils, eosinophils, and basophils) -  and most importantly monocytes - which mature into macrophages.


Hence the name Granulocyte-macrophage colony-stimulating factor.


Already GM-CSF is used to treat humans dealing with neutropenia (low white cells), which may arise as the result of chemotherapy, radiation treatment, viral infections, or bone marrow diseases.


Whether GM-CSF turns out to be a viable treatment for influenza or not, this type of cutting edge research into the workings of the immune system will likely lead to new treatments for influenza, and hopefully other diseases as well.

1 comment:

Anonymous said...

A great introduction to the publication on GM-SCF!

I wonder if hamster would be a better model than the mouse for such study.