This article greets you during the height of flu season. As I drove by a local retailer last fall, I noticed it displayed a large advertisement for free flu shots. (The only time the thought of a flu shot enters my mind is when I drive by such signs, or hear about them on the news. Like many people, I have never received a flu shot, and have no future plans to drop by the "retail giant" and get one.)
Flu Symptoms
Each fall, masses of people believe that the flu virus will once again be set loose and wreak havoc on those who happen to get in its path. Accordingly, many flock to get flu shots for the purpose of "preventing" the flu. All this really means is that they want to avoid being plagued for a week by high fever, coughing, nasal congestion, fatigue, malaise and headaches - symptoms we associate with the flu. Diagnosis is typically rendered by symptoms alone. So, if you have these symptoms, you supposedly have the flu.
The serious flaw with the classic tale of flu prevention is that we hear nothing about the nature of the host unlucky enough to develop the flu symptoms. We typically hear about the host who is "susceptible" because of a weakened immune system, one that supposedly allows for the flu to develop. I'm referring to the type of person, and immune-weakening, that we think enters the chiropractic office. Personally, I have a hard time believing in this type of "immune inhibition," and suggest that it has probably never existed.
My view obviously runs contrary to the standard treatment. Most people sincerely believe that colds and the flu develop because of some type of immune-inhibiting encounter, which renders us susceptible to a virus or bacteria; or a direct encounter with a virus that simply overwhelms our system. The latter is a common perception as it relates to the flu, which is why so many run to get their flu shots.
The Missing Flu Link - Overactive Immune System Causes Flu Symptoms
It seems that flu symptoms may actually develop because of an "overactive" immune system, not one that is depressed. All flu symptoms can be related to immune system stimulation, rather than inhibition. To understand this connection, we need to know a little about cytokine biology.
Cytokines are defined as molecules of cell communication. The term "interleukin" is used to describe one of the subfamilies of cytokines. Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) are examples of cytokines that are pro-inflammatory and are thought to play a role in immune stimulation. These cytokines are released from immune cells, such as macrophages, in response to injury; infection; poisons; immune complexes; and other cytokines.1
IL-1 and TNF stimulate:
- an increase in production of IL-l, TNF and other cytokines from macrophages and other immune cells;
- white cells to release pro-inflammatory free radicals;
- atherogenic process in endothelial cells;
- fibrogenic activity in fibroblasts; and
- the acute-phase response.1
What is the acute-phase response? Biochemically, it is associated with an increase in the production of acute-phase proteins, such as C-reactive protein, serum amyloid, complement and coagulation proteins. With respect to signs and symptoms, it is characterized by general hyperalgesia and allodynia; fever; increased sleep; decreased appetite; shivering; chills; malaise; somnolence; depression; memory loss; reduced social interactions; reduced aggressive behavior; and reduced sexual activity.
1,2 Are these not the exact signs and symptoms one has when diagnosed with the flu?
Clearly, the flu is nothing more than an acute-phase response. And remember, a "flu" diagnosis is done by symptoms alone. So, we need to consider that perhaps the acute-phase response may not be caused by the influenza virus, and that there may be other inducers of the response. One thing is certain: We are suffering from immune activation, not inhibition.
Research on the Acute-Phase Response
Maier and Watkins published perhaps the most readable paper on the acute-phase response.2 IL-1 is particularly potent at generating the acute-phase response, and research has demonstrated that peripheral administration of IL-1 leads to all features of the acute-phase response. Additionally, this results in the induction of IL-1 production in the hypothalamus and hippocampus. It is this central induction of IL-1 (and TNF and IL-6) that leads to the acute-phase response.
To understand the physiological process that generates the acute-phase response, it is important to first know that modern anatomical studies have revealed that about 70% of vagal fibers are afferent - quite different than what is presented in standard neuroanatomy books. With this in mind, consider that, upon stimulation (injury, infection, etc.), peripheral macrophages release cytokines that activate vagal afferents (located in the gut, liver and spleen), which terminate in the nucleus tractus solitarius (NTS) located in the medulla. The NTS then projects to the hypothalamus and hippocampus, and this results in CNS production of IL-1, which leads to the induction of the acute-phase response or flu-like symptoms.2
Research has demonstrated that the acute-phase response induced by peripheral IL-1 administration could be abolished by cutting the vagus nerve,2 so there is no question that the sickness response is neurologically generated. Research has also demonstrated that afferent input from laminae I, IV-VII and X project to regions of the NTS very close to vagal afferents. This means that somatic nociceptive afferents will ultimately lead to activation of the NTS-hypothalamus-IL1 cascade, resulting in an acute-phase response. Consider, for example, that flu-like symptoms can develop if you are out of shape and decide to engage in heavy exercise.
Acute-Phase Foods and the Holiday Nutritional Nightmare
Nutritional research is clear when it comes to cytokine generation. It is known that omega-6 (n6) fatty acids (linoleic acid and arachidonic acid) increase macrophage release of IL-l and TNF, while omega-3 (n3) fatty acids have the opposite effect.3,4 James, et al., state that supplementation of fish oil (which contains the n3 fatty acids EPA and DHA) in healthy controls and rheumatoid arthritis patients has resulted in up to 90% inhibition of IL-1 and TNF.3
Future articles will discuss additional nutritional considerations in relation to cytokine modulation, but suffice it to say that antioxidants and bioflavonoids can also inhibit cytokine activity. So, lots of fruits and vegetables, green tea, olive oil, and anti oxidant supplements such as lipoic acid; coenzyme Q10; vitamin E; curcumin; and resveratrol can help reduce cytokine induction.
For the time being, let's consider our holiday dietary issues. There is really no better way to put it: Holidays are basically an "omega-6 fatty-acid fest." From Halloween to Easter, we literally gorge ourselves on bread, pastries, cakes, grains and the n6 seed oils (corn, sunflower, safflower) present in these and other packaged foods. Compare, for example, your own ingestion of the above foods to n3-rich, leafy green vegetables during the period extending from Halloween to Easter. Is this not the time of year that many of us gain 5-10 additional pounds? We certainly don't pack on these pounds because we eat too much salad and broccoli; instead, we gorge ourselves with "acute-phase foods."
Some might argue that we gain weight and get sick from too much sugar, and this certainly plays a role, for a reason you may be unaware of. Consider that sweets can also be considered "acute-phase foods." A recent study indicated that hyperglycemia acutely increases circulating cytokine concentrations; in particular, IL-6, IL-18 and TNF.5
There is no escaping the fact that the holiday stretch of months is an inflammatory bonanza. "Acute-phase foods," rich in omega-6 fatty acids and with high glycemic indices, are the rule during this time of year.
Experts believe that we need a one-to-one ratio of n6:n3 fatty acids in our diet, and the average American boasts a 20-30:1 ratio, which is exceedingly inflammatory. There is no question that holiday eating helps to drive this imbalance and the related acute-phase response.
Conclusion
Numerous insults can stimulate our immune cells into action. Trauma, toxins and even autosuggestion (although not mentioned here) can stimulate cytokine release and the acute phase response. The flu is nothing more than an acute-phase response, and without appropriate testing, we cannot state that the presence of an acute phase response confirms a flu virus infection. The holidays are stressful in many ways, and any number of stressors are capable of inducing an acute-phase response. We only augment this possibility by ingesting enormous amounts of "acute-phase foods" during this time of year.
During this holiday season, try avoiding the "acute-phase foods," increase your intake of fruits and vegetables and increase your supplementation with n3 fatty acids and antioxidants.
References
- Contran RS, Kumar V, Collins T. Robbins Pathologic Basis of Disease, 6th ed. Philadelphia: WB Saunders, 1999:74,86.
- Maier SF, Watkins LR. Cytokines for psychologists: implications of a bidirectional immune-to-brain communication for understanding behavior, mood, and cognitions. Psychol Rev 1998;105(1):83-107.
- James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 2000;71(suppl):343S-48S.
- Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999;70(suppl):560S-69S.
- Esposito K, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans. Circulation 2002;106:2067-72.
