Can a too hygienic childhood lead to crippling adult diseases? Might a vaccine treat depression? 

         Perhaps it already has.

         Researchers at the Royal Marsden Hospital in London, prominently reported in the Economist, vaccinated lung cancer patients with mycobacterium vaccae.  Mycobacteria greatly interest physicians, as different forms cause tuberculosis and leprosy.  It was hoped the patients would show cancer remission.  They did.  They also become considerably less depressed.

         Chris Lowry, a professor at Bristol University, wanted to know why.  As humans are highly inconvenient subjects for brain experiments, he studied mice.  They too were vaccinated with mycobacterium vaccae.

         The mice showed predictable increases in cell mediated immune chemicals, called cytokines.  Cytokines do a lot of things.  They are blamed in part for heart disease, diabetes, and the inflammatory response that is the causative agent of death in many infectious diseases – which cytokines also fight.

         Dr. Lowry found connections between cytokines and sensory nerves that run to the brain.  Some of these cells directly secrete serotonin into brain areas critical to emotional function and stress response.  Such increases in serotonin are thought to the reason why many popular antidepressants, like Prozac, work.

         Though you can study depression in mice, it’s highly indirect.  Stress reduction is much easier to follow.  Mice, particularly when stressed, don’t like being thrown into water.  They react the way many non-swimming humans do who feel they are drowning.

         The mice vaccinated with mycobacterium vaccae liked swimming.  Stress was much reduced.

         There are many ironies to mycobacteria vaccinations decreasing depression. In the 1950’s, different antitubercular drugs were tried out on that period’s usual study subjects – mental patients and prisoners.  The side effects of many of these medications were awful. However, one anti-TB drug turned out to make many of the chronically depressed patients a lot happier.  From this medication were born the first effective modern anti-depressants, the monoamine oxidase inhibitors, or MAOIs.  Though most today think the antidepressant effect came from direct changes to neurotransmitters, was immune manipulation a reason they work?

         Studies like those of Dr. Lowry are causing many people to wholly rethink disease causation.  One preliminary hypothesis is that many illnesses, ranging from cancer to heart disease, are caused by inflammation.  The type and intensity of the inflammation determines what end organ gets hit.

         Inflammation is increased in many conditions.  Most pulmonologists will tell you sleep apnea is a breathing disorder.  But Alex Vgontzas, a professor at Penn State, looked further.

         He knew that people with sleep apnea had high levels of cytokines, marking a higher inflammatory state.  He gave patients with severe sleep apnea were given drugs that block tumor necrosis factor alpha, an important cytokine.

         By all rights, patients with a weight related “breathing disorder” should have seen no effect.  Yet their rates of apnea decreased by 20%.  More interestingly their level of daytime sleepiness improved as much as with CPAP, the mechanical gold standard treatment for sleep apnea. 

         Many conditions cause increases in inflammatory cytokines.  Obesity is one.  Diabetics show major changes in inflammation.  Inflammatory changes in arterial lining cells cause plaque, probably the main immediate cause of heart attacks and strokes.

         Immune function starts in the womb.  However, maternal antibodies, available through breast milk and cells left in the infant, have a major effect on fighting infectious diseases.  However, the infant also has to be exposed to the diseases to create that immunity.

         For many years neurologists have hypothesized that having “too clean” a childhood environment might predispose to multiple sclerosis, long thought to hit upper class children disproportionately.  Now researchers think that too much hygiene may be partly to blame for the worldwide increases in asthma and allergy incidence.  It may be impossible to be too rich or too thin, but is it possible to be too clean?

         Immunity and the brain have been connected by researchers for decades. Yet research in many illnesses have had blinkers on for far too long.  These will be exciting times for systems biology, where the myriad interactions of immune, neurological, rehumatological, cardiac, and renal systems will finally get the attention they deserve.  Much of disease and health is about how information is processed in the body, how these many different systems cross-talk and interact. Not only are they highly interrelated, they are strongly affected by the overall environment. That means factors like what we eat, how we move, how we talk, who are friends are.  The connections in many case are subtle, and will require new ways of understanding and modeling data.

         Yet someday we may treat our low moods and arthritis by going out and playing in dirt enriched with healthy bacteria.  Perhaps gardeners always knew that.

Dr. Matthew Edlund, M.D., M.O.H., director of The Center for Circadian Medicine, is an expert on applied public health, sleep medicine and psychiatry. A former professor at Brown and University of Texas medical schools, he can be reached via email to DocME@DoctorEdlund.com. And CLICK HERE to subscribe to our new Fitcast, via the iTunes Store.