Heavy metal exposure and the human immune system

The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods
Original source: Journal of Occupational Medicine and Toxicology 2008, 3:25
Authors: Nasr YA Hemdan
Publication date: 6 November 2008
DOI (digital document ID): 10.1186/1745-6673-3-25
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
Heavy metals are known to affect the actions of T-helper (Th) cells and thereby affect the development of illnesses and disease. Interleukin (IL)-12, a crucial one of these cells, is one of the Th cells affected by outside agents. IL-12 promotes systemic inflammation and affects the body's response to disease. The author is testing to see if IL-12 levels are affected by heavy metal exposure.

Tests were run using both cultured human immune tissues and live mice. The human cells were cultured without exposure to either cadmium (Cd) or mercury (Hg). The mice were continuously exposed to sublethal doses of Cd or Hg salts for 3 or 5 weeks. Several different methods were used to evaluate the IL-12 levels.

IL-12 levels were dependent on levels of exposure to Cd or Hg, and on interferon-gamma (IFN-gamma) levels. The various measurement approaches were considered equally valid. In the absence of heavy metals, the interaction between IL-12 and IFN-gamma was shown to depend on the disease microorganism to which the cells were exposed.

Reliability:
The author is associated with several accredited institutions and appears to specialize in immunology. The tests were run redundantly using several different methods and came out the same each way, suggesting accuracy in the results received. The study was published in a peer-reviewed journal. The number of subjects (both human and rodents) was not explicitly stated, so it is difficult to tell if the results may be skewed by small sample size.

Practical Applications:
We are increasingly exposed to heavy metals and other environmental toxins; these are now shown to depress our immune systems. One of the difficulties in living long-term with diabetes is that the immune system is compromised. (Type 1 diabetes is an autoimmune disease.) This suggests that people with diabetes may need to be more careful than non-diabetics in minimizing our exposure to heavy-metal toxins. (Certain fish are known dietary sources of these toxins.)

I was curious to find out if the author had made any correlation between heavy-metal exposure and the development or progression of autoimmune disease. (He did not.)

This synopsis was based on the entire article.

A possible reason for increased risk of infection of obese people and those with Type 2 diabetes

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus
Original source: International Journal of Obesity (2008) Vol. 32, pp. 1407–1414
Authors: G R C Zilverschoon, C J Tack, L A B Joosten, B J Kullberg, J W M van der Meer and M G Netea (corresponding author)
Publication date: published online 22 July 2008
DOI (digital document ID): doi:10.1038/ijo.2008.109
Requires subscription? Not for this article
Publicly-available abstract: Yes

Synopsis:
Interleukin-18 (IL-18) is a signalling chemical (similar to hormones) that has a strong effect on stimulating interferon (IFN) release. It is produced by a number of different white blood cells and central nervous system cells. Interferon is an important chemical in fighting infections.

Higher levels of IL-18 have been shown to decrease abnormally large appetite and to improve insulin sensitivity. Interestingly, several studies have shown high levels of IL-18 in obese people with insulin resistance, and a recent study has demonstrated that a common version of the genes producing IL-18 is associated with a higher body mass index (weight) in people with type 2 diabetes or coronary heart disease. In addition, weight loss after bariatric surgery (such as gastric bypass or lapband) results in lowered blood concentrations of IL-18.

The investigators suspect that the cells of obese people and those with insulin resistant diabetes may have high levels of IL-18 because they do not respond as well to IL-18 as those of people of normal weight and who are not diabetic. To test this theory, they tested white blood cells of obese and Type 2 diabetes patients and compared them to those of lean, non-diabetic people, and measured their IFN production in relation to their IL-18 levels. They found that in the obese and the diabetic subjects, these cells respond poorly to IL-18 and produce less interferon. They also show impaired release of IFN after exposure to disease-carrying bacteria and fungi.

They conclude that the reduced response to IL-18 may be responsible for the increased susceptibility to infection among those who are obese or who have Type 2 diabetes.

Reliability:
The study was conducted with a small number of subjects: seventeen control subjects, eleven obese non-diabetic subjects, and fourteen subjects with Type 2/insulin-resistant diabetes. (The possibility of LADA or other autoimmune diseases was ruled out at the start of the study.) The smaller the number of subjects, the greater the possibility for skewed or atypical results. The research was published in a peer-reviewed journal, and the investigators are all associated with the a University Medical Center in the Netherlands. Based on the small number of subjects, the results should be considered to point in the direction of larger studies to confirm the investigators' results, as well as further research into why these cells have an impaired reaction to IL-18.

Practical Applications:
A confirmed pathway and reason for increased risk of infection among obese people and people with Type 2 diabetes could lead to therapy to reduce that risk and to better fight those infections that do occur. If insulin resistance and excessive appetite are also directly related to impaired IL-18 response, then improving that response could conceivably result in weight loss and improved insulin sensitivity as well.


This synopsis was based on the entire article.