Friday, July 25, 2008

PAMP and Circumstance



# 2175



Today we have an interesting study from Yale, published in the Journal of Clinical Investigation, suggesting why cigarette smokers are more apt to suffer greater ill effects, or even die, from viral respiratory infections.


The study:


Cigarette smoke selectively enhances viral PAMP– and virus-induced pulmonary innate immune and remodeling responses in mice

Min-Jong Kang1, Chun Geun Lee1, Jae-Young Lee1, Charles S. Dela Cruz1, Zhijian J. Chen2, Richard Enelow1 and Jack A. Elias1,3



. . . was performed on mice, since it wouldn't be ethical to infect humans with potentially lethal viruses.   



As you might guess from the title, this is a complex, and very technical journal article.  Unless you are a physician, a biologist, or a masochist you may not choose to wend your way through this entire study.  



Luckily, we have a synopsis even I can understand.





But first, a little background on PAMP, our innate immune system, and how all of this may relate to pandemic flu.  


Relax, I promise I'll be gentle.


Each of us is born with what we call Innate Immunity, or a generic immune response that is not pathogen-specific.  


As we are exposed to various viruses, our bodies learn to recognize them, and create pathogen-specific antibodies against them - this is called acquired immunity.


For our innate immunity to work, it must have a way to recognize an infective agent, even from a virus it has never seen before. 


Here is where PAMPs come in.  


PAMPs (Pathogen-Associated Molecular Patterns) are patterns of molecules associated with many types of pathogens.


In other words, PAMPs are an easily recognizable signature that tells our innate immune system that we have been infected . . . with something.  


Our immune systems have cells designed to recognize, and react to these signatures.   We are born with this ability, and they keep us alive while our bodies learn to recognize and fight new infections.


Our innate immune responses involve the following cells (taken from Doc Kaisers Microbiology Course)


  • phagocytic cells (neutrophils, monocytes, and macrophages);
  • cells that release inflammatory mediators (basophils, mast cells, and eosinophils);
  • natural killer cells (NK cells); and
  • molecules such as complement proteins, acute phase proteins, and cytokines.


In other words, our innate immune system throws just about everything but the kitchen sink at an unrecognized infection.  


In response our bodies spike a fever while natural killer cells and phagocytes rush to fight the infection.  Our bodies produce protein and cytokine rich fluids at the site of the infection and cells throughout our body release inflammatory mediators.   


Generally all of these things are good things, as they help fight the viral invader, although they are what make us so miserable when we have the flu.  


These immune responses, particularly with respiratory infections, can also make our lungs ideal breeding grounds for bacterial infections.


Bacteria that normally live dormant and unnoticed in our lungs suddenly find a nutrient rich broth building up in the lungs, and warmer temperatures, courtesy of a fever.    Practically overnight they can bloom.


This is why secondary bacterial pneumonia is a common complication of a viral respiratory infection. 


During a pandemic caused by a novel influenza virus, it will be our innate immune system that will react to any infection.  We will have very little acquired immunity (unless the virus shares some component with a previously circulating  influenza virus).  


How our innate immune system responds to this novel infection will determine, in large measure, our fate.



Now that I've set the stage, we can now proceed on to the Yale Study.



Simply put, we've always known that cigarette smokers fare far worse with respiratory infections than non-smokers.  The assumption has been that smokers have a dampened immune response, and therefore are unable to combat a viral invader.  



This study suggests just the opposite.   That smokers mount a much stronger immune response via their innate immune system, than non-smokers.   And it is this hyper-response that causes the trouble.



I'll let this article from Medical-News Today carry on.



Yale Study Shows Why Cigarette Smoke Makes Flu, Other Viral Infections Worse

Article Date: 25 Jul 2008 - 1:00 PDT


A new study by researchers at Yale School of Medicine could explain why the cold and flu virus symptoms that are often mild and transient in non-smokers can seriously sicken smokers. Published in the Journal of Clinical Investigation, the study also identified the mechanism by which viruses and cigarette smoke interact to increase lung inflammation and damage.


Until recently, scientists haven't been able to explain why smokers have more exaggerated responses to viral infections. Smokers have been more likely than non-smokers to die during previous influenza epidemics and are more prone to chronic obstructive pulmonary disease (COPD). Furthermore, children who are exposed to second-hand smoke have more severe responses when infected with respiratory synctial virus.


The prevailing view has been that cigarette smoke decreases anti-viral responses. But the Yale researchers-lead author Jack A. Elias, M.D., the Waldermar Von Zedtwitz Professor of Medicine and chair of internal medicine at Yale School of Medicine, and first author Min-Jong Kang, M.D., associate research scientist-found the opposite to be true.


Their experiments showed that the immune systems of mice exposed to cigarette smoke from as little as two cigarettes a day for two weeks overreacted when they were also exposed to a mimic of the flu virus.


The mice's immune systems cleared the virus normally but the exaggerated inflammation caused increased levels of tissue damage.

"The anti-viral responses in the cigarette smoke exposed mice were not only not defective, but were hyperactive," said Elias. "These findings suggest that smokers do not get in trouble because they can't clear or fight off the virus; they get in trouble because they overreact to it."


"It's like smokers are using the equivalent of a sledge hammer, rather than a fly swatter, to get rid of a fly," said Elias.

(Continued . . .)






Another good reason to give up cigarettes.   As if we needed another.


And as a former smoker myself, I recognize how tough quitting can be.    I was about as addicted as you can get to them.   I grew up with smokers, was married twice to smokers, and finally succumbed to the habit myself in my late 30's.    


Stupid, I know. 


I tried repeatedly to quit, without success.   The physical cravings were my undoing.   Then, 14 months ago, I tried  Chantix.    I was off cigs in a week, and never looked back. 


I know it doesn't work for everyone, and some people have had unpleasant side-effects.    If you are considering it, you need to consult with your doctor.   And you need to be ready to quit. 


I can only say that it worked for me. 


Gary Near Death Valley said...

Nice to know that had quit also. I started smoking after high school and when I was a logger for 3 years. Then I joined the fire service and it seemed most of the fire personnel smoked. Remember that, when you came out of a smoking building,,,,,,,,,,and pulled out a pack or bummed one sat on the tail board and smoked. Well I smoked gee from about 11965 to 1990 when at a neighbors playing cards, had a heavy chest discomfort, stood up, had a sharp pain down my left arm, and immediately broke out in a sweat.
Having been a medic on a fire dept rescue I knew something was going on with my heart and I had the neighbor call for an ambulance within 30 seconds of the onset.

As I lay on the gurney in the emergency room, a doctor leaned over reading my chart, and told me that it would be a good idea that I quit smoking. I did that right then and there. Yep had a heart attack but was back on duty full time in two months,,,,and smoke free.

Oh the pleasures that we give up!

monty said...

EXCEPT, and this is important, in the case of cytokine storm in the lungs, especially re novel H1N1's perhaps greatest cause of mortality. While smoking generally makes people people fare worse w/ viral respiratory infections -- pretty obvious: they get sicker, take longer for symptoms to resolve, etc. -- nicotine, which has anti-inflammatory action, in the lungs has been demonstrated in preliminary but solid studies to reduce inflammation in the lungs (probably why way back when physicians used to prescribe tobacco smoking for asthma patients and it actually worked in a lot of cases) and reduce or reverse the severity of cytokine storm. At any rate, now would probably not be the optimal time to quit smoking: Nicotine withdrawal causes significant inflammation in the lungs -- that's where all that hacking up stuff comes, continuing a couple weeks to a month, even more, after a person quits; mix nicotine withdrawal w/ novel H1N1 infection, even if you're not adolescent or post-adolescent, you might wind up in real trouble.