What are Cytokines?

Cytokines are proteins that signal cells to act throughout the body. They are inflammatory in nature and are classified as proteins, peptides, and polypeptides (a nice pictorial of cellular immunity at work). One commonly known cytokine, interferon type I is used to treat hepatitis B and C.

There is debate in the scientific community whether or not cytokines are hormones. This may be due in part to their anatomy, origin, and level of concentration in the body. Cytokines can be concentrated 1,000s times greater during trauma or infection. Hormones are generally secreted by localized organs/glands such as the pancreas while cytokines can be generated from nearly every nucleated cell in our body including macrophages (WBCs), endothelial cells (interior of our body) like those that line our blood vessels, and epithelial cells (surface of our body) like our skin.

Here is a video representation courtesy of nucleusinc.org:

Just thinking about the structure of cytokines brings to light the fact that they are all highly dependent upon adequate levels of cholesterol since cell membrane structural integrity and intracellular communication are all reliant on cholesterol. In addition, WBCs act immunoprotectively with cholesterol in the blood to bind to and inactivate toxins such as bacteria, viruses, fungi, and free radicals. Here is a good site with practical application tips to reduce inflammation while enhancing the body’s immunoprotective abilities naturally without dependence drugs which are partly responsible for iatrogenic disease and death. This also highlights one way cholesterol plays a role in immunity and how it may relate to other diseases such as cancer (McCully, Ravnskov & Rosch, 2011).  

Cytokines are active in both acute and chronic inflammation. This is a two edged sword since they actively facilitate immune responses in our body. Chronic inflammation can have detrimental long-term impact on our health and should be minimized since inflammation is a contributory factor in cardiovascular disease. This may be how statins are protective by reducing C-reactive protein (CRP) an inflammatory marker, needless to say the harm associated with statin’s cholesterol lowering effect is greater than its documented benefits.

There are many factors that stimulate chronic inflammation and this is the underlying issue we should seek to correct when considering any level of prevention. Addressing these health abnormalities through a symptomatic response (pharmaceuticals) can have untold long-term consequences including cancer.

The greatest benefit of acute inflammation occurs when we have an infection. Inflammation stimulates cholesterol production. The bad news is that as chronic inflammation continues it inhibits nitric oxide (NO), a potent vasodilator, increases blood pressure and places the lining of our blood vessels at increased risk through atherosclerosis. The mechanisms responsible for atherosclerosis are very complex and the presence of cholesterol does not necessarily indicate cause. One of statins’ benefits comes from inflammation reduction. According to Chris Masterjohn, (he describes the process in great detail here), statins can provide a co-occurring negative impact by reducing Coenzyme Q10 production which works in conjunction to NO to improve cardiovascular function and negate the effects of atherosclerosis. Statins are also known to cause muscle degeneration. Think about your heart. It is a muscle.

We need cytokines to keep us healthy when we get sick. We also need to understand how chronic inflammation occurs and to moderate the its effects by our lifestyle choices. When trying to mitigate these risks, understanding what causes inflammation and how to prevent it can reduce the risk of health problems down the road. We should approach it though our diet and lifestyle not a drug . . . unless you want to take that risk.


McCully, K., Ravnskov, U., and Rosch, P. (2011). The statin-low cholesterol-cancer conundrum. Quarterly Journal of Medicine. doi: 10.1093/qjmed/hcr243

Low Total Cholesterol and Mortality Rates

This is an exploration of mortality rates associated with low cholesterol. The review was published in Circulation: Journal of the American Heart Association. In this review, the National Heart, Lung, and Blood Institute held a conference seeking to understand why lower total cholesterol (TC) levels are associated with some cancers, respiratory and digestive diseases, trauma, and residual deaths.

Apparently, men are more susceptible to this correlation than women. They examined 19 cohort studies from the U.S., Europe, Israel, and Japan. TC is a calculation of cholesterol measurements of LDL, HDL, and triglycerides.  The review noted high rates of cerebral hemorrhage with lower average TC. The rate of cerebral hemorrhage decreased as average TC went up in prospective populations. This was true in the Multiple Risk Factor Intervention Trial (MRFIT) in addition to increased incidence of colon cancer with lower TC. This may be related to what I wrote in an earlier post.

For women, 6 of the 11 studies showed no variation in cancer death rates across all spectrum of TC levels. There was an increased cancer risk in men when their TC levels fell below 180 mg/dL. In non-cancer and non-cardiovascular death rates, both men and women had similar risk findings. When TC was below 160 mg/dL there was a 40% increase of mortality compared to 160-199 mg/dL levels. Risk was also reduced by 10% when TC levels were between 200-240 mg/dL compared to the reference class (TC between 160-199 mg/dL levels).

This increase in non-cardiovascular deaths raises the issue of the dangers associated with taking cholesterol lowering drugs. These dangers are real and should not be taken likely (as mentioned in the study). Once again, when the data was pooled together, TC below 160 mg/dL was associated with highest risk of mortality.

Unfortunately, some of the data did not differentiate between age or sex but we can assume that having TC this low for anyone is quite risky. The review did take into account people with diabetes, smokers, CVD, alcohol intake, and other possible factors that might skew the data. Some of the research also separated participants further by age and gender.

Findings for all-cause mortality (ACM [death from any cause]) for those with TC between 200-240 mg/dL had the lowest incidence. The rate of death increased the TC went down below 199 mg/dL (are you seeing a trend yet?). Interestingly enough, the American Heart Association, the journal’s parent organization, say that total cholesterol should be below 200 mg/dL. This is the range that has been demonstrated by the AHA to increase risk death from all causes. The standard protocol for primary care providers is to prescribe statin medication when TC is above 200 mg/dL which will place patients well within the range of increased risk of death. 

There are also other health risks associated with direct effect of statin use in addition to health benefits not associated with TC lowering mechanisms. Statins act on many mechanisms in addition to reducing cholesterol synthesis in the liver. A benefit-risk analysis of statin use will be explored in a future post.

It is safe to say that total cholesterol levels appear safest when they remain in the range between 200-240 mg/dL. This is my target. Unless you have a very rare disease, it is completely controllable through diet which will be discussed later. Don’t forget exercise will increase your total cholesterol level (by increasing HDL) as it improves your health.