The Double-Edged Sword of Inflammation

By Dillon Lim - Medicine Student @ Brasenose College, Oxford

 

Inflammation is an important physiological response to injurious (causing damage) agents, helping to contain and eliminate them. The problem with the mechanisms of this response is that they necessarily cause some collateral damage for the host organism even when appropriately activated, and there are unfortunately many conditions associated with an inappropriate activation of inflammation. Let’s talk through some of the main aspects of inflammation, and then about some cases where it can go wrong.


Thus, inflammation is a response to perceived damage, whether caused by a pathogen, physical trauma, or even potentially a self-antigen. There are molecular (some key proteins) and cellular (white blood cell) components to this response, driven by signals called cytokines. The key hallmarks of acute inflammation were given Latin names a few centuries ago and are sometimes still referred to in textbooks by them: rubor (redness), calor (heat), tumor (swelling), dolor (pain) and functio laesa (loss of function). The release of histamine, among other things, causes a local dilation and an increase in permeability of blood vessels around the injury/infection and is responsible for our redness, heat and swelling. This allows the molecular/cellular components to leave the blood and enter the tissue.


Molecules such as members of the complement cascade are effective at killing bacteria. Other chemical mediators released activate pain-sensing nerve endings. Some white blood cells interact with the injurious agent directly – neutrophils, for example, are good at phagocytosing, or engulfing and digesting, bacteria, and certain types of T-cells are able to interact with and induce the death of virally-infected cells. Others still act by releasing biomolecules: B cells of course are known for their production of antibodies. The loss of function (and to some extent the pain) is essentially caused by damage to cells caught in the crossfire of this soup of inflammatory mediators. Chronic inflammation usually progresses after a failure of acute inflammation to contain the (perceived) damage and can stretch for months and years.


The collateral damage done by white blood cells is particularly problematic in some chronic conditions such as tuberculosis and hepatitis. These diseases are both initially caused by a pathogen but the main damage effects of the pathology are actually effected by our own immune systems. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, hides out in our own macrophages and is able to escape most of the acute inflammatory response. They then get combatted with a “granulomatous” inflammation, which essentially involves immune cells walling off infected cells in the lungs. The damage to the lung tissue this causes leaves the lungs stiff, and makes them difficult to inflate. In hepatitis, we’ve actually been able to show that by killing off a type of T cell we can delay the onset of symptoms – it seems counter-intuitive, but it goes to show how dangerous the immune system can be.


The immune system is also sometimes misdirected – either against self-antigens or against foreign but harmless (e.g. pollen, peanut) antigens. One of the most extreme examples of autoimmunity is systemic lupus erythematosus (SLE, or lupus for short), where the immune system is activated against our own DNA and the proteins associated with it. Neutrophils, which we mentioned earlier, sometimes break down to expose their genetic material during acute inflammation – and it is thought that it is this exposure (which occurs during a perfectly normal, appropriate inflammatory response) that triggers the development of lupus. Allergic reactions range from the annoying (a rash) to the life-threatening (anaphylactic shock), and is associated with histamine release. Massive release of histamine causes constriction of the airways and a drop in blood pressure.


Further reading:

  1. A Double-Edged Sword: Inflammation and Your Health. https://www.cedars-sinai.org/discoveries/inflammation.html

  2. Inflammation: A Double Edged Sword. https://aor.ca/inflammation-a-double-edged-sword/

  3. Inflammation in tuberculosis: interactions, imbalances and interventions. https://www.sciencedirect.com/science/article/pii/S0952791513000757 (Advanced)

  4. CD8+ T Cells Mediate Viral Clearance and Disease Pathogenesis during Acute Hepatitis B Virus Infection. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC140637/ (Advanced)