November 2014 

Inflammation and its discontents

When cells of the immune system encounter invading germs they can become activated and enter into a heightened state of alert. Such cells help to marshal the immune system against germs. Here is a greatly simplified response by the immune system to an infection:

  • Chemical signals are released that attract other cells of the immune system with specialized functions to where the invading germs are concentrated.
  • As the number of  immune system cells increases at the site of infection, some of these cells try to contain the germs.
  • Other cells take a molecular picture of the invading germ and then travel to lymph nodes and lymphatic tissues where they warn the immune system about the invader.
  • As a result of these actions, the immune system becomes activated and lymph nodes and lymphatic tissues make many copies of CD8+ cells—the body’s premier infection-fighting cells. These CD8+ cells are released into circulation to attack germs and kill infected cells.
  • The body raises its temperature to try to kill germs.
  • Usually all of these immune responses help to contain an infection, and as the number of germs decreases, the immune system releases anti-inflammatory signals and other cells that specialize in suppressing the immune system to dampen its responses.

However, when the immune system is not able to control and vanquish an infection, a state of activation persists. We discuss the consequences of this persistent activation later in this article.

Where is the immune system?

The immune system is located in several organs and tissues such as the thymus gland, spleen and bone marrow. There are also many lymphatic tissues and lymph nodes scattered throughout the body between the neck and the knees, particularly around the intestines. Also, cells of the immune system are distributed throughout the body and found in other major organ-systems, including the brain, heart and blood vessels, kidneys, liver, lungs and so on. The emplacement of cells of the immune system in these different organ-systems serves to provide local protection for them.

In cases of chronic infection when the immune system remains activated, its inflamed cells release chemical signals that in turn cause inflammation in the organ-systems where they are resident. Thus, inflammation is transferred to other parts of the body. Temporary inflammation during short-lived infections is useful for marshalling the immune response and nutrients to feed the creation of millions (perhaps even billions in some cases) of new cells. However, chronic inflammation from ongoing infection—such as that arising from HIV—can injure organ-systems, causing them to slowly degrade.

Researchers are finding that in HIV-negative people excessive levels of inflammation appear to play a role in the injury associated with many health conditions, and perhaps even in the cause of some conditions, including the following:

  • arthritis
  • obesity
  • psoriasis
  • cardiovascular disease
  • diabetes
  • higher-than-normal blood pressure
  • cancer
  • thinning bones

It is possible that inflammation may also play a role in HIV-positive people when the above-listed conditions occur.

Reducing inflammation

Studies have found that taking combination anti-HIV therapy (commonly called ART or HAART) greatly reduces the level of HIV-related inflammation. However, because ART does not cure HIV infection, some degree of excess inflammation persists. Scientists are therefore conducting studies to try to find ways to safely suppress the excess inflammation that occurs in HIV-positive people

In this issue, we review some studies that explore ways to help dampen HIV-related inflammation among ART users. Future issues of TreatmentUpdate will also report on HIV-related inflammation.

—Sean R. Hosein


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