IFN pathway produces interferons but also inhibits the production of KC and Mip2

IFN pathway produces interferons but also inhibits the production of KC and Mip2

ResearchBlogging.orgThe H1N1 flu has now been circulating for over 3 months and has landed on every continent (Antarctica doesn’t count as a continent in the medical world), infecting thousands of people. People continue to die at a steady pace and yesterday a girl in Brazil died with atypical symptoms (yes it is in Portuguese, but I’ll summarize what it says here).

This girl had contracted a pneumococcus infection and ended up dying from septicemia.  The physicians speculate that her contraction of H1N1 may have lowered her immunity to a pneumonia infection, leaving her vulnerable to the bacteria.

Although the science is still out on this issue there is a model that has been presented about why those infected with influenza are at an increased risk for secondary pneumococcus infections.  An article in the Journal of Clinical Investigation seems to pinpoint the reason for the increased risk of secondary infection.

The scientists proposed that when the body responds to a viral infection there is a concurrent loss in the ability to respond to bacterial infections.  Type I IFN receptors were targeted because they are a large part of the innate response to viral infections.  When activated they produce a cascade of cytokines that act to inhibit viral replication.  This is the early response the body takes as it goes through the process of antibody production and maturation (maybe one of the most fascinating subjects in immunology).  The researchers found that when mice had their Type I IFN receptors knocked out there was a much higher level of KC and Mip2, two chemoattractants used to recruit neutrophils to the site of bacterial infection.

So it looks as though the Type I IFN receptors inhibit the production of KC and Mip2.  This would cause far less neutrophils to be found at infection sites in mice responding to an influenza challenge, which is what the researchers saw.

This is another key in developing a model of how one branch of the immune response can mediate activity of another branch of the system.  It is complicated though as it has been shown that influenza proteins can inhibit the production of IFN, which would also inhibit the activation of the IFN receptors and subsequent products.

Secondary pneumococcal infection also only occurs in a subset of individuals so there are still parts of this story that need to be elucidated.  But this does give immunologists a working model for this system of infections and as can be seen from the case in Brazil maybe help to stop further infections in the future.

Shahangian, A., Chow, E., Tian, X., Kang, J., Ghaffari, A., Liu, S., Belperio, J., Cheng, G., & Deng, J. (2009). Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice Journal of Clinical Investigation, 119 (7), 1910-1920 DOI: 10.1172/JCI35412


Get ready for it. The BBC has a report about General Practitioners staying away from work if there is a crisis with the H1N1 pandemic. It may not be long before everyone is tired of the media saturation concerning “death-in-service.”  But it sounds as though the UK does have a bit of a problem of their hands.  According to Dr. Dean Marshall, unless physicians die on a day when they are at work, their families will not be paid out.  From the BBC:

“For locum doctors, of which there are several thousand, the situation is further complicated by arrangements for death-in-service payments.

Under current arrangements, pay-outs to family would be made only if the doctor died during days when they were working.

Dr Marshall said: ‘A locum could die at the weekend and their family might not get a pay-out. That is not fair and could make some think twice about helping out.”‘

Ouch, I would stay home as well if I was faced with that sort of loophole in my coverage and protection of my family.  A deal needs to be worked out soon in order to stop this from becoming an issue before it is too late and the UK is staring down a dangerous pandemic while still trying to negotiate with their physicians.  Interesting what type of issues this pandemic has brought up in the health community, from surveillance to employee protection.

Thanks to the link via H5N1.

Just hours after the WHO declared a Level 6 alert for the novel H1N1 outbreak a business local to the Chicago area declared that they may be coming into a $150 to $200 million windfall.  Baxter International released a statement concerning orders of the H1N1 vaccine and how the WHO’s decision to move to Level 6 will create a huge cash supplement this year.  According to Chicago Business:

Several countries have contracts with Deerfield-based Baxter and other drug makers that reserve the right to buy vaccines if the WHO declares a Level 6 pandemic. A number of governments now are likely to exercise those advance-purchase agreements, New York-based J. P. Morgan Chase & Co. analyst Mike Weinstein said in a research note to clients.

Baxter has stated that it will be ready to fulfill orders in October.  The UK, the only country to publicly announce a vaccine purchase, will buy up to 30 million doses from Baxter with the rest coming from GlaxoSmithKline.

World leaders have been worried that a Level 6 declaration will cause widespread panic and hurt businesses around the globe, especially those dealing with tourism or entertainment.  While that is a possibility it does not relenquish the duty of the WHO to make factually informed decisions concerning the information it passes onto the global community.  National health organizations such as the CDC watch and follow what the WHO presents in order to evaluate measures to take to deal with pandemics and it is of utmost importance that the WHO maintain independence from political pressure in order to provide the most accurate and detailed information they can.

Level 6 has been declared and there were not riots on the streets, there were no businesses who immediately closed their doors, and there were no borders that were shut down.  It is most likely that this virus will affect business around the world but I think that would happen regardless of what the WHO does.  Local newspapers and large media corporations do a pretty good job of covering what the clinics are seeing and do more to fan fears than present relevant information.  That is why the WHO needs to step up and be that provider that gives the real information that we as a global community need to combat these types of outbreaks.

Another aspect of this move is that we don’t get many opportunities to practice our containment and treatment protocols for novel pandemic infections.  We are very lucky in that this virus is not a “killer” and the shortcomings of our response systems aren’t pointed out by mass hospitalizations and mortality rates.  This is why surveillance is going to be so key with this outbreak.  The epidemiologists and infections disease experts are going to have to comb over all the details to give good recommendations on how we can upgrade our systems so when the real thing comes along we are sure we are doing everything in our power to stop it in its tracks.