Understanding Inflammation

In developed countries, some of the most intractable medical problems are not related to infection, but rather inflammation. It’s hard to watch TV and not see ads for drugs for Rheumatoid Arthritis (inflammation of joints), Asthma/allergies (breathing pathways), Atherosclerosis (blood vessels), or Inflammatory Bowel Diseases (intestines).

But what is inflammation? And what are the treatment strategies to control it?

Inflammation

Inflammation is actually a good thing. It’s how our body fights infections, cleans up damage, and start healing tissue. In our body’s desire to protect us, however, it sometimes acts too hastily or tries to do too much. And an overactive immune system can unfortunately cause not only intense pain, but also irreversible damage.

Trigger and Response

Because of its intense powers, inflammation needs to be triggered. These triggers are usually molecular patterns in bad things, like bacteria and toxin, that the body has adapted to notice. However, in patients with allergies/asthma, harmless things like pollen, dander, foods can trigger inflammation. In patients with autoimmune conditions (i.e. Lupus, Rheumatoid Arthritis, Multiple Sclerosis), the body identifies its own cells as foreign and attacks.

There are sensor cells (dendritic cells, macrophages) located in all parts of the body that look for these patterns and alert the body to an intruder. They release chemical signals that trigger local inflammation. These signals increase blood flow to the area, allow circulating white blood cells - our first-line soldiers - to leave the bloodstream and attack. They also trigger the body to make and train more first-responder soldiers just in case. This is called acute inflammation because it happens immediately, and for many bad things, this response is enough.

However, if the first-line soldiers can’t get the job done, the sensor cells can move to our immune central commands (lymph nodes) and trigger our most powerful weapons - lymphocytes - to multiply and mobilize. This is called chronic inflammation because it occurs in both longer-lasting infections or chronic inflammatory disorders.

In both acute and chronic inflammation, after we kill the bad guys, there’s usually a lot of damage that needs to be cleaned up and tissue that needs to be repaired. The body redeploys the first- and second-line soldiers away and triggers the diplomats (macrophages) to repair and rebuild the tissue.

Treatment Strategies

Now that you get the gist of inflammation, you can understand the methods we use to treat it. It’s more important to understand the logical framework than the individual drugs, but I listed them since you probably use them regularly or might see ads for them on TV. Now you’ll know how they work!

(A) Block the inflammatory signals

Logically, the easiest thing we can do is just prevent inflammation from being triggered. We do this all the time to treat things like headaches and hangovers.

Aspirin, Advil (ibuprofen) and Tylenol (acetaminophen) are good examples. They inhibit the production of a signal needed for an inflammatory response. So by blocking its production, we can reduce inflammation.

For allergies specifically, another important chemical signal is called histamine. It is released by mast cells in tissues in response to allergies and mediates a lot of the same things locally as prostaglandins. To prevent this, the easiest thing we can do is prevent it from acting on other cells. Antihistamines like Benadryl and Claritin do this.

Lastly, for more serious conditions, we sometimes also want to block the systemic chemicals that trigger even bigger responses. For these, we make big proteins called antibodies that identify these chemicals in the blood and stop them dead in their tracks. Examples of these are Remicade and Embrel.

(B) Counteract the inflammation

What if inflammation is already taking place? The first approach won’t work as well to alleviate acute symptoms. In this case, we want to identify the discomforting symptom - and counteract it.

For example, in asthma, inflammation leads to muscular constriction of the tubes (bronchi) that bring air into the lungs. People having an asthma attack don’t have time to waste - they need those tubes opened up quickly.

Albuterol is the mainstay that acts on the same muscles as the inflammatory process, but it triggers a different process, eventually leading to dilation and relief.

In allergies, the thing that disturbs people the most is nasal congestion. The blood vessels around the nose, stimulated by inflammation, dilate to bring in more fluid to the sinuses. To combat this problem, we can just counteract the vessel dilation. Sudafed (Pseudoephedrine) does just that.

(C) Block the production and unleashing of the powerful weapons (lymphocytes)

Sometimes, we can’t control inflammation by blocking the signals. We have to be more aggressive. What makes inflammatory disorders devastating is the action of those really powerful weapons - those lymphocytes. What if we blocked their production? And if they are already in the blood, why don’t we block their function?

And that’s what we do. Some drugs block the ability of ANY fast growing cell (lymphocyte included) from proliferating. Other drugs aim to selectively block the function of the lymphocytes themselves.

(D) Give em steroids

For decades, a mainstay of treatment for inflammatory disease has been steroids. Leading the pack is Prednisone. But there are many others and are used in different circumstances. These are the drugs that do a little bit of everything, from (A) → (C). Because they are both effective and potentially destructive, these are used very judiciously. In some conditions, they are first-line. In others, they are last resort.

Conclusions

As you can see, inflammation has the power to act heroically, but also the power to cause great harm. With that power comes the responsibility to act judiciously. When the response is not commensurate to the challenge, we get an inflammatory disorder that needs to be addressed. By understanding the process of inflammation, we can understand the strategies health professionals use to treat them.