The immune system and endometriosis

You have probably read a lot about the immune system and endometriosis. If after reading any of the scientific articles on the subject you've been confused, then join the club.

The literature on the immune system and endometriosis is esoteric, confusing, and frequently contradictory. Beyond that, the literature on this subject usually commits Sin #4 of the endometriosis literature: the conclusions are usually bent to try to support Sampson's theory of reflux menstruation as the origin of the disease.

Dr. Redwine's "Sins of the endometriosis literature"

  1. Lack of knowledge of multiple visual appearances.
  2. Attention directed at infertility rather than pain.
  3. Conclusions drawn from response of symptoms rather than from response of the disease.
  4. Attempt to support Sampson's theory of reflux menstruation at all costs, despite the absence of evidence for initial attachment.
  5. Surgical therapy results are the opinions of the surgeon, not validated by biopsies or follow-up studies.

An immune system review

Let's review a little about the immune system. It is the functional system of our bodies that identifies self from non-self by using certain characteristics on the surface of a cell. By "feeling" a cell, the immune system determines whether this cell belongs in a certain area or not. If it does not belong, then the immune system goes into action to eliminate the foreign cell. These actions are largely controlled by white blood cells, although circulating antibodies are also important.

Some white blood cells have the ability to kill foreign cells immediately, while other white blood cells have to be recruited and trained to kill intruders. Recruited white blood cells are called to the site of battle by chemicals released by injured tissue or by other white blood cells.

While engaged in local battle, the body also mounts a more systemic reaction, with substances appearing in the bloodstream in reaction to inflammation and injury. Thus, a scientist has the ability to measure several main varieties of normal immune responses to injury: groups of white blood cells as well as local and systemic inflammatory chemicals and hormones. Primary effects, or secondary?

The immune system obviously is important in everything that goes on in the body and one can expect to see changes with any alteration of health. The problem is trying to determine whether the immune system changes that have been found with endometriosis are primary (meaning you are born with them) or secondary (meaning they are the result of injury due to endometriosis), or perhaps a little bit of both.

My guess is that a little of both is what is going on, with the real damage resulting from Sin #4. The decreased natural-killer cell activity reported especially in advanced stages of endometriosis seems likely to be a primary defect, since this seems to remain even after endometriosis is treated. The local and systemic production of reactive chemicals seem likely to be secondary to inflammation and injury, since the immune system is just doing its job.

Why would it be surprising that women with such an irritative process as endometriosis in their pelvis have more inflammatory cells, chemicals and fluid in their pelvic cavities? Yet these normal immune system responses have been highlighted as being somehow important in an immune origin of endometriosis, rather than just the normal, healthy immune system at work.

Substances which affect the immune system adversely, such as dioxin or radiation, have been found to be associated with an increased frequency and severity of endometriosis in experimental animals, although a recent report failed to find an effect of polychlorinated biphenyls in monkeys. Environmental toxins such as these are primarily products of the late 20th century, however, and endometriosis has been known to exist long before that.

How the immune system is supposed to let endometriosis occur

Here's how people are trying to put the round peg of the immune system into the square hole of origin of endometriosis. The theory is that during the monthly menstrual flow, some of the endometrial cells from the lining of the uterus are swept in reverse with menstrual blood out of the fallopian tubes. The blood and cells drip into the pelvis, where the endometrial cells attach to the peritoneal surfaces, aided and abetted by a deficient immune system.

It is postulated that "normal" women with "normal" immune systems have a type of immunologic warfare going on which allows their immune systems to kill the refluxed cells. (The obvious question here would be: Has anyone found evidence of such immunological warfare going on in the pelvis of "normal women," since this alleged process plays such an important role in the theory of the immune system and endometriosis? Don't bother to ask such a question, no one has looked for this obvious piece of the puzzle.)

Since the endometriosis patient is supposed to have such a decrepit immune system (although actually the immune system response to endometriosis has been shown to be largely normal, vigorous and appropriate) the endometrial cells are not attacked and are allowed to remain attached whereupon they can implant, proliferate and grow into endometriosis.

The fatal leap of faith of this theory remains the apparent continuing absence of abundant evidence that initial attachment of endometrial cells ever occurs. Endometrial cells are said to be attaching by the billions and billions around the world on any day, yet convincing evidence of the initial attachment of these cells is lacking.

This should be incredibly easy proof to come by - you could take biopsies of the pelvic peritoneum at random and if you took enough biopsies, you should find evidence of endometrial cells attached to the pelvic surfaces everywhere. Yet, none of the papers on "microscopic" endometriosis of the 1980s and 1990s has found evidence of a single attached endometrial cell among the dozens and dozens of patients studies.

Why is something that is supposedly occurring all the time so difficult to find? (Maybe because it doesn't occur in the first place?) Even if the facilitative immunodeficiency model were correct, there still is no immune therapy available based on this model. Some researchers are pointing to the immunomodulating effects of danazol as possibly being important in immunotherapy of the disease. However, danazol has been around for almost a quarter of a century. If danazol were the answer, we could stop here and go home.

Finally, if the immune system of endometriosis patients were truly decrepit, other problems should be seen. Yet cancers, infections, and autoimmune disease do not seem to be more prevalent among women with endometriosis, and it is a rare patient who came to my practice for surgery complaining of chronic yeast infections.