Understanding acute inflammation. *Hint* It’s actually part of a normal response to injury!
Often when we hear the word ‘inflammation’ our immediate response is that inflammation is negative. We may think ‘pain’, ‘ageing’ or ‘disease’.
While it can at times wreak havoc in our body, inflammation is actually part of our body’s immediate immune response against injury and infection.
Inflammation is therefore a protective mechanism, and while it may feel uncomfortable at the time, it’s a vital part of the healing process.
The problems we associate with inflammation are when it overreacts or overstays it’s welcome.
Below we will discuss the inflammatory response associated with musculoskeletal injury and how we differentiate between an inflammatory response that is performing a helpful role in healing, versus inflammation that exists beyond tissue repair that is driving an ongoing pain response.
The three lines of defence
To understand inflammation, we need to understand the immune system.
There are three primary lines of defence that protect us against foreign invaders:
Physical barrier and chemical barriers
Non-specific internal defences
The adaptive immune response
The first line of defence prevents pathogens entering the body in the first place. This includes our skin, our mucous membranes, secretions such as tears and saliva, and our stomach acid.
An example of a breach of this would be a skin laceration, a bee sting or an airborne pathogen entering our respiratory tract, resulting in a chest infection.
The second line of defence is a series of non-specific responses that target any foreign invader, regardless of type.
This response is rapid but doesn’t help to build long-term immunity. This is also referred to as our innate immune response.
Inflammation is part of this second line - rapid, yet non-specific.
Fever, and other cellular responses (e.g. phagocytosis, the ingestion of bacteria) occur during this phase.
The innate immune response begins when immune cells sense distress signals from damaged or dying cells, triggering inflammation to contain and repair the injury.
It can also be activated by microbial patterns such as bacterial cell wall components or viral RNA that alert the body to infection.
While the innate immune system provides rapid, non-specific protection, the body’s most sophisticated defence lies in the third line: adaptive immunity.
Unlike the first two lines, this system learns and remembers.
Specialised lymphocytes (B cells and T cells) identify specific pathogens, destroy infected cells and produce antibodies tailored to the invader. Memory cells remain after the infection, ensuring a faster, stronger response if the same threat returns.
What is inflammation and what is its purpose?
As described above, inflammation is the body’s natural response to injury or infection.
What we are typically referring to here is ‘acute inflammation’, which will respond quickly when we cut ourselves, sprain a ligament, injure a bone or when an infectious agent breaches our first line of defence.
‘Acute’ means that it is short-term and its purpose is healing. The goal of inflammation is to remove the cause of injury and initiate repair – not to cause harm.
The inflammation some may think of when they hear that word, is chronic inflammation - which is long-term, damaging inflammation that behaves differently to acute inflammation.
Our discussion here is concerned with acute inflammation, as it is a key feature of musculoskeletal injury and it’s important to consider the best approach to managing this inflammatory response.
Acute inflammation is a defensive, vascular response to pain or injury. It mobilises the necessary cells and molecules from our circulation to the site where they are needed.
These cells serve to remove the initial cause of injury and clean up the debris associated with cell death or tissue damage.
This early clean-up response is needed to make way for the formation of new and healthy tissue at the site of repair.
Inflammation and our body’s natural healing response
Under normal circumstances, we can leave inflammation to do its job. Provided we don’t exacerbate the injury further, the inflammatory response will subside within days to weeks as the tissue repairs fully.
The advice concerning the management of soft tissue injuries has shifted in recent years, as we have started to appreciate the utility of acute inflammation in initiating a quick healing response.
Stifling this natural process by applying ice or consuming NSAID’s will likely just delay tissue repair. You can learn more about that here.
In fact, a recent meta-analysis examining the practice of cold water immersion post-exercise demonstrates the negative implications of intervening on our body's natural recovery cycle.
Though the effect is small, this review showed that cold water immersion immediately post training led to reductions in potential muscle hypertrophy.
Although not strictly related to inflammation, the possible mechanisms by which this might limit muscle growth is the reduction of cell signalling, the lowering of blood flow and nutrient delivery, and the possible alteration of the inflammatory response.
This is not to say that cold water immersion doesn’t have a role in recovery or an overall wellness program. It may even be that timing of cold water immersion is the important factor, and to introduce it outside of that immediate recovery window may prove beneficial.
These interventions aimed at reducing pain and limiting excessive inflammation, may subdue the helpful inflammatory response that is paving the way towards full tissue repair.
What triggers an acute inflammatory response?
There are several drivers that initiate inflammation in the body. These include physical tissue damage (such a sprain or break), infection, disease and metabolic stressors, and a stress response.
An example of tissue damage:
Skin cut or abrasion: breaks the protective barrier, releasing danger signals and attracting immune cells.
Muscle strain or tear: damaged fibres release DAMPs, leading to localised swelling and pain.
Sunburn: UV radiation damages skin cells, causing them to die and release inflammatory signals.
Burns (thermal or chemical): severe tissue injury activates an intense inflammatory response.
Fracture or bone injury: broken bone and surrounding tissue release signals that recruit immune cells for repair.
Ischemia (restricted blood flow): lack of oxygen damages cells, triggering inflammation when blood flow returns.
Infections that may trigger an acute response (though these can develop into chronic infection and inflammation):
Bacterial infection (e.g. strep throat): inflammation clears once the infection is treated.
Viral infection (e.g influenza): fever and aches resolve after the virus is cleared.
Fungal infection (e.g athlete’s foot): usually acute at onset, though can become chronic if untreated.
Diseases that drive inflammation will typically be classified as chronic.
The key cells involved in acute inflammation
When tissue is damaged or invaded by pathogens, the body rapidly mobilises a specialised team of cells to address and rectify the issue to bring the body back to homeostasis.
Each cell plays a unique role in identifying, attacking or clearing the problem so that repair work can begin.
Neutrophils: the first responders
Neutrophils are the dominant cell type in acute inflammation and the first to arrive at the site of injury.
These white blood cells are equipped with granules containing potent enzymes and reactive oxygen species that destroy bacteria and break down cellular debris by engulfing them.
When tissue damage is slight, an adequate supply of these cells can be obtained from those already circulating in the blood.
But when damage is extensive, stores of neutrophils (some even in immature form) are released from the bone marrow where they are generated.
Neutrophils are the most important agents of response to pyogenic bacterial infections (pus-forming) and are the initial responders to most types of mechanical or physical injury.
Basophils
Basophils are a type of white blood cell. They protect your body from invaders.
They also trigger allergic reactions to allergens and infections by releasing histamine to improve blood flow to damaged tissue.
Basophils cells also release heparin to prevent blood from clotting in an area that has sustained damage. Blood needs to reach the area so it can heal.
Eosinophils
They are less prominent in acute musculoskeletal inflammation but play a defensive role against parasites and contribute to allergic responses.
Mast cells
Release histamine and other chemicals that increase vascular permeability and attract other immune cells.
Mast cells are located at the boundaries of tissues and the external environment – such as the mucosal surfaces of the gut and lungs, the skin and around blood vessels.
Macrophages
Although macrophages are more often associated with chronic inflammation, they are also essential during the resolution phase of an acute inflammatory response.
Monocytes migrate from blood to tissue to become macrophages. They then engulf dead neutrophils, debris and pathogens, and release growth factors that promote tissue repair.
They act as a bridge between inflammation and healing.
Molecular mediators of inflammation
There are also several molecules that play an important role in mediating inflammation, which we will look at in greater detail in another post.
These include cytokines, chemokines and prostaglandins.
Inflammatory signalling pathways
The various ways in which these molecules coordinate with the immune cells listed above is known as our ‘inflammatory signalling pathways’ and bear a great influence on the outcome of inflammation.
The cardinal signs of inflammation
So, what does inflammation look like to the naked eye?
Aulus Cornelius Celsus (25 BC-50 AD), a Roman encyclopedist, offered a still valid statement about inflammation: “Notae vero inflammationis sunt quatuor: rubor et tumor cum calore and dolore”, defining the four cardinal signs of inflammation as redness and swelling with heat and pain.
And while long considered as a morbid phenomenon, John Hunter (18th century) and Elie Metchnikoff (19th century) understood that it was a natural and beneficial event that aims to address a sterile or an infectious insult.
There are four (plus one more) physical signs of acute inflammation. These are:
Rubor (redness)
Cause: increased blood flow (hyperemia) to the affected area due to the dilation of small blood vessels (arterioles and capillaries).
Why it happens: the body sends more blood to deliver immune cells and nutrients to the site of injury or infection.
Tumor (swelling)
Cause: accumulation of fluid (edema) in the tissues.
Why it happens: blood vessels become more permeable, allowing plasma proteins and white blood cells to leave the bloodstream and enter the tissue, which helps fight infection and start repair, but also causes swelling.
Dolor (pain)
Cause: release of chemicals (like prostaglandins and bradykinin) that stimulate nerve endings.
Why it happens: These chemicals sensitise nerves, making the area more sensitive to pain. Swelling can also physically press on nerves, contributing to discomfort.
Calor (heat)
Cause: increased blood flow to the area raises the local temperature.
Why it happens: the warmth is a direct result of more blood (which is warmer than surrounding tissues) being delivered to the site.
Functio laesa (loss of function)
Cause: the four effects of inflammation as stated above.
Why it happens: the four effects combine to create a temporary loss of function.
These physiological changes are part of the body’s defence mechanism. They help bring immune cells, antibodies and nutrients to the site of injury or infection, and facilitate the removal of debris and pathogens.
Once the threat is eliminated and repair is underway, these changes subside, and the tissue gradually returns to normal.
The sequence of events in acute inflammation
So, how do the components of this immune response all work together? Let’s step through the way these events occur in the body.
The trigger
Tissue damage or invading pathogen.
Detection
Resident immune cells (e.g. macrophages or mast cells) detect danger by either recognising the unique physical structure of a pathogen or by recognising the outcome of injured tissues.
Vasoconstriction
A temporary vasoconstriction may occur in some cases to limit blood loss (i.e. in the case of a flesh wound).
Release of chemical mediators
The inflammatory signalling pathways commence. These activated immune cells release histamine, prostaglandins, leukotrienes and cytokines, which begin communicating with blood vessels and other immune cells.
Vascular changes
In response to histamine, vascular channels to the site of injury widen. Blood vessels increase their permeability, causing exudation (leaking) of plasma proteins and fluid into the tissue.
Pain
Some of the released mediators (e.g. bradykinin) both activate pain receptors and increase sensitivity to mechanical pain.
Leukocytes arrive at site of injury
The mediator molecules alter the blood vessels to permit the flow of neutrophils and macrophages into the tissue.
The neutrophils migrate along a chemotactic gradient created by local cells to reach the site of injury.
The action of these cells is outlined above.
Amplification
When necessary, the inflammatory response will be increased through signalling pathways (primarily the action of cytokines).
Resolution
Once the threat is sufficiently cleared or a reparative process has commenced, inflammation will begin to subside.
If the inflammatory stimulus persists or the body’s immune regulation fails, inflammation can transition from acute to chronic, with longer-lived immune cells taking over.
So, should we be actively reducing inflammation when it occurs?
Acute inflammation is adaptive and necessary for repair.
As mentioned above, early suppression of the inflammatory process can delay healing (by reducing cell migration and tissue repair).
However, when inflammation is excessive (causing pain/swelling that impedes movement), temporary relief measures can be helpful. The key to this is timing and moderation.
As osteopaths, our role is to support the body’s natural healing processes. Manual therapies on their own don’t ‘heal’ but they do aid in the speed and comfort of the body’s natural healing process.