Fever vs Inflammation

Fever vs Inflammation

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What's the difference between inflammation and fever? And why is fever called an inflammatory response? Does the word inflammation have both a general and a specific meaning?

Inflammation includes accumulation of inflammatory cells, such as neutrophils or macrophags, in a tissue. The typical four local signs of inflammation include redness (Latin rubor), heat (calor), swelling (tumor), and pain (dolor) (Britannica).

Fever is a symptom, which may or may not be present in a certain inflammatory condition. For example, lung inflammation in pneumonia is usually accompanied with fever, while joint inflammation in rheumatoid arthritis is not.

Inflammation? Fever? What to expect after your second COVID-19 vaccine shot

By Nicole Karlis
Published April 5, 2021 10:00AM (EDT)

A healthcare worker receives a dose of Pfizer-BioNTech Covid-19 vaccine (Wong Fok Loy/SOPA Images/LightRocket via Getty Images)


Every day, millions of people in the United States are getting the COVID-19 vaccine. And as more shots end up in more arms, more questions arise—especially for the two-shot vaccines, which are still the majority of the vaccines distributed in the United States.

Anecdotally, many of the vaccinated report fatigue or even faint fevers after receiving their second shot. Podcaster Ellie Schnitt said she felt like she was "on her death bed" after her second shot. Producer and TV writer Scott Derrickson said he felt "like he had Covid" after his second dose.

Indeed, while it is certainly possible to experience side effects after dose one, there's a higher frequency of side effects after the second dose, according to clinical trial data for both vaccines.

The vaccines that require two shots are the two from Pfizer and Moderna, which are both approved in the United States and are both made using messenger RNA, or mRNA. This mRNA technology delivers the genetic code of one of the virus's proteins to one's cells. The immune system learns recognize the spike protein on the SARS-2 coronavirus and develop antibodies to fight it. While both vaccines use the same technology, there are a few differences between the two.

First, the Pfizer vaccine has been authorized for people aged 16 and older Moderna has been approved for people 18 and older. However, both companies are conducting vaccine trials for those in lower age groups. Second, both vaccines have remarkable efficacy Pfizer is at 95 percent, and Moderna was 94.1% effective at preventing symptomatic COVID-19 cases. Another major difference is the time between receiving the first and second dose— the second Moderna dose is 28 days. For the Pfizer vaccine, it's 21 days. This is partly because Moderna administers a larger first dose— 100 micrograms. The Pfizer dose contains 30 micrograms of the vaccine.

Salon interviewed Dr. Amesh Adalja, a Senior Scholar at the Johns Hopkins Center for Health Security, to answer some of readers' most pressing questions on how to prepare for one's second shot, and what to expect. As always, this interview has been condensed and edited for clarity.

Should people take time off of work for a day or two, or let their bosses know that they'll be getting the second dose, in case they're not feeling well?

I wouldn't necessarily preemptively take a day off, but I would probably let people know that you're getting a vaccine and just to be a little more understanding and maybe flexible about that, because it's unpredictable. I know people who have had a second dose and had no problems at all. I myself had a second dose and went and worked an overnight shift in the ICU afterwards. I felt a little achy, but it was fine. And then there are other people who have more severe symptoms, so I think it really is variable. I would just let people know that that's what's happening. And have some flexibility built into that.

Fatigue is a common side effect. For the Moderna vaccine, the highest rate of fatigue reported were by trial participants 18 to 64 years after the 2nd dose. More than half of Pfizer trial participants reported fatigue after the second dose, too. But people are wondering, how much fatigue should they expect to experience? Is it possible that too much fatigue would be alarming, and someone should call their doctor if they're experiencing it?

Some people spend the day in bed, and other people feel tired but they still go about their day. I think it's variable.

It's usually just you feel tired, you feel more sleepy than normal, that's basically how most people experience it. It's hard to know exactly how much the fatigue is concerning because it's such a subjective type of complaint, and also depends on your baseline and other medical conditions that you may have. I would say for the 36 or so hours post-vaccine that it's probably normal to feel fatigue after that. If it continues then I think it may be something else unrelated to the vaccine, or something you might need to be formally evaluated for. I don't think there's any hard and fast rule to come up with, because you have to kind of look at each person's baseline and understand where they fit.

Are there any side effects people should keep their eye on after the 15 minute observation period is over?

The 15 minutes period is meant to screen out people that might have severe allergic reactions. Severe allergic reactions are unlikely to occur after that period of time. You may still have the aches and pains. Some people with the Moderna vaccine get a rash several days later at the injection site. Some people do get those Moderna rashes evaluated by their doctors, but it's not something that requires you to call 911.

People have asked if they can take over the counter medicine after they received the vaccine — say, Ibuprofen and Advil. What are your thoughts on that?

I took acetaminophen (which is Tylenol) about 12 hours, or maybe 18 hours, after the second dose because of a headache, some muscle aches and pains. I think it's completely fine to do that.

There are some theoretical concerns about using non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, which brand names are Advil or Motrin or Aleve, because they think it might blunt the immune response. There have been some studies with other vaccines, but I don't know if it's clinically significant. But for people that have that concern, you could take acetaminophen, or Tylenol — it's not an anti-inflammatory drug.

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What about drinking alcohol? There have been some reports of people in other countries being advised not to drink after receiving the vaccine.

I don't think it makes a big clinical difference. The only thing I would say is just be careful with alcohol and then blaming the vaccine for your hangover. You know, or if you get nausea and vomiting or you get a headache because you're hung over.

Another side effect is swollen lymph nodes.

That's not necessarily just a second dose side effect, that can happen anytime. A lot of these things could happen with either, but yeah, you can get swollen lymph nodes. After a vaccination, that's not uncommon. It happens with other vaccines as well.

That's one of the sites of your immune system, where it's housed, so it's not uncommon to see that increased activity of your immune system be correlated with increased lymph node swelling, which is usually transient and goes away just like when you get swollen lymph nodes after a sore throat, for example.

When the lymph node swells, the one that swells is closest to where the site of inflammation is in the site of inflammation. The site of inflammation with this vaccine is your deltoid muscle, which is going to drain to your axillary lymph node, so the lymph nodes in your armpits. So those are the ones that you wouldn't you'd maybe see get full in versus the ones in your neck which you get sometimes after, you know, what, when you have strep throat.

Some people have wondered, "if I'm not having any side effects is the vaccine working?"

You can't make that kind of a claim. In general, when you do have those side effects it is the result of your immune system but the absence of those side effects doesn't mean that you're not getting a take, or we call say "the vaccine is not taking." We can't really say that some people have no symptoms at all with the vaccine and they have a perfectly appropriate response to it, immunologically.

Do either the Moderna or Pfizer vaccine have more side effects than the other?

These weren't studied in head to head trials, so it's very hard to make comparisons.

Markers of Inflammation

Inflammation is a complex and necessary component of the response to biological, chemical, or physical stimuli, and the cellular and molecular events that initiate and regulate the interactions between the various players in the inflammatory process remain a source of ongoing investigation. In the acute phase of the inflammatory response, cells of the immune system migrate to the site of injury in a carefully orchestrated sequence of events that is facilitated by soluble mediators such as cytokines, chemokines, and acute-phase proteins. Depending on the degree of injury, this acute phase may be sufficient to resolve the damage and initiate healing processes. Persistent inflammation, either as a result of prolonged exposure to stimulation or an inappropriate reaction against self-molecules, can lead to the chronic phase, in which tissue damage and fibrosis can occur. Chronic inflammation has been reported to contribute to numerous diseases, including arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, and cancer, and to conditions of aging. Hematology and clinical chemistry data from standard toxicology studies can provide an initial indication of the presence and sometimes the location of inflammation. These data may suggest more specific immune function assays that are necessary to determine the presence and/or mechanism(s) of immunomodulation. Although changes in hematology dynamics, acute-phase proteins, complement factors, and cytokines are common to virtually all inflammatory conditions, and can be measured by a variety of techniques, individual biomarkers have yet to be strongly associated with specific pathologic events. Thus, although sensitive indicators of inflammation, these factors generally lack the specificity to identify the offending cause. The profile seen in a given inflammatory condition is dependent on the severity, chronicity, and mechanisms involved in the inflammatory process, as well as the species and the capacity of the individual's immune system to respond and adapt.

Keywords: Acute-phase proteins Basophil Chemokine Clinical pathology Complement Cytokine Eosinophil Hematology Inflammation Lymphocyte Macrophage Monocyte Neutrophil Platelet.

Cardinal Signs

There are five cardinal signs of inflammation, though it may also cause additional symptoms if severe.

Inflammation can cause pain in joints and muscles. When inflammation is chronic, a person will experience high levels of pain sensitivity and stiffness. The inflamed areas may be sensitive to touch.

With both acute and chronic inflammation, pain is the result of inflammatory chemicals that stimulate nerve endings, causing the affected areas to feel more sensitive.

When inflamed areas of the body feel warm, it is because there is more blood flow in those areas. People with arthritic conditions may have inflamed joints that feel warm to the touch. The skin around those joints, however, may not have the same warmth. Whole-body inflammation may cause fevers as a result of the inflammatory response when someone has an illness or infection.


Inflamed areas of the body may appear red in color. This is because blood vessels of inflamed areas are filled with more blood than usual.


Swelling is common when a part of the body is inflamed. It is the result of fluid accumulating in tissues either throughout the body or in the specific affected area. Swelling can occur without inflammation, especially with injuries.

Loss of Function

Inflammation may cause loss of function, related to both injury and illness. For example, an inflamed joint cannot be moved properly, or it can make it difficult to breathe due to a respiratory infection.

The reason for all these symptoms is the same: Cytokines released into the bloodstream lead to increased vascular permeability to allow migration of immune cells into tissues.

Fighting Inflammation

Chronic inflammation plays a central role in some of the most challenging diseases of our time, including rheumatoid arthritis, cancer, heart disease, diabetes, asthma, and even Alzheimer&rsquos. This report will examine the role that chronic inflammation plays in these conditions, and will also provide information on the breadth of drugs currently available to alleviate symptoms. Drug choices range from simple aspirin, a nonsteroidal anti-inflammatory drug that&rsquos been available for more than a century, to disease-modifying drugs and so-called biologics that promise more targeted treatments.

17.5 Inflammation and Fever

The inflammatory response, or inflammation , is triggered by a cascade of chemical mediators and cellular responses that may occur when cells are damaged and stressed or when pathogens successfully breach the physical barriers of the innate immune system. Although inflammation is typically associated with negative consequences of injury or disease, it is a necessary process insofar as it allows for recruitment of the cellular defenses needed to eliminate pathogens, remove damaged and dead cells, and initiate repair mechanisms. Excessive inflammation, however, can result in local tissue damage and, in severe cases, may even become deadly.

Acute Inflammation

An early, if not immediate, response to tissue injury is acute inflammation . Immediately following an injury, vasoconstriction of blood vessels will occur to minimize blood loss. The amount of vasoconstriction is related to the amount of vascular injury, but it is usually brief. Vasoconstriction is followed by vasodilation and increased vascular permeability, as a direct result of the release of histamine from resident mast cells. Increased blood flow and vascular permeability can dilute toxins and bacterial products at the site of injury or infection. They also contribute to the five observable signs associated with the inflammatory response: erythema (redness), edema (swelling), heat, pain, and altered function. Vasodilation and increased vascular permeability are also associated with an influx of phagocytes at the site of injury and/or infection. This can enhance the inflammatory response because phagocytes may release proinflammatory chemicals when they are activated by cellular distress signals released from damaged cells, by PAMPs , or by opsonins on the surface of pathogens. Activation of the complement system can further enhance the inflammatory response through the production of the anaphylatoxin C5a. Figure 17.23 illustrates a typical case of acute inflammation at the site of a skin wound.

During the period of inflammation, the release of bradykinin causes capillaries to remain dilated, flooding tissues with fluids and leading to edema. Increasing numbers of neutrophils are recruited to the area to fight pathogens. As the fight rages on, pus forms from the accumulation of neutrophils, dead cells, tissue fluids, and lymph. Typically, after a few days, macrophages will help to clear out this pus. Eventually, tissue repair can begin in the wounded area.

Chronic Inflammation

When acute inflammation is unable to clear an infectious pathogen, chronic inflammation may occur. This often results in an ongoing (and sometimes futile) lower-level battle between the host organism and the pathogen. The wounded area may heal at a superficial level, but pathogens may still be present in deeper tissues, stimulating ongoing inflammation. Additionally, chronic inflammation may be involved in the progression of degenerative neurological diseases such as Alzheimer’s and Parkinson’s, heart disease, and metastatic cancer.

Chronic inflammation may lead to the formation of granuloma s, pockets of infected tissue walled off and surrounded by WBCs. Macrophages and other phagocytes wage an unsuccessful battle to eliminate the pathogens and dead cellular materials within a granuloma. One example of a disease that produces chronic inflammation is tuberculosis , which results in the formation of granulomas in lung tissues. A tubercular granuloma is called a tubercle (Figure 17.24). Tuberculosis will be covered in more detail in Bacterial Infections of the Respiratory Tract.

Chronic inflammation is not just associated with bacterial infections. Chronic inflammation can be an important cause of tissue damage from viral infections. The extensive scarring observed with hepatitis C infections and liver cirrhosis is the result of chronic inflammation.

Check Your Understanding

  • Name the five signs of inflammation.
  • Is a granuloma an acute or chronic form of inflammation? Explain.

Micro Connections

Chronic Edema

In addition to granulomas, chronic inflammation can also result in long-term edema. A condition known as lymphatic filariasis (also known as elephantiasis ) provides an extreme example. Lymphatic filariasis is caused by microscopic nematodes (parasitic worms) whose larvae are transmitted between human hosts by mosquitoes. Adult worms live in the lymphatic vessels, where their presence stimulates infiltration by lymphocytes, plasma cells, eosinophils, and thrombocytes (a condition known as lymphangitis). Because of the chronic nature of the illness, granulomas, fibrosis, and blocking of the lymphatic system may eventually occur. Over time, these blockages may worsen with repeated infections over decades, leading to skin thickened with edema and fibrosis. Lymph (extracellular tissue fluid) may spill out of the lymphatic areas and back into tissues, causing extreme swelling (Figure 17.25). Secondary bacterial infections commonly follow. Because it is a disease caused by a parasite, eosinophilia (a dramatic rise in the number of eosinophils in the blood) is characteristic of acute infection. However, this increase in antiparasite granulocytes is not sufficient to clear the infection in many cases.

Lymphatic filariasis affects an estimated 120 million people worldwide, mostly concentrated in Africa and Asia. 2 Improved sanitation and mosquito control can reduce transmission rates.


A fever is an inflammatory response that extends beyond the site of infection and affects the entire body, resulting in an overall increase in body temperature. Body temperature is normally regulated and maintained by the hypothalamus, an anatomical section of the brain that functions to maintain homeostasis in the body. However, certain bacterial or viral infections can result in the production of pyrogens , chemicals that effectively alter the “thermostat setting” of the hypothalamus to elevate body temperature and cause fever. Pyrogens may be exogenous or endogenous. For example, the endotoxin lipopolysaccharide (LPS) , produced by gram-negative bacteria, is an exogenous pyrogen that may induce the leukocytes to release endogenous pyrogens such as interleukin-1 (IL-1), IL-6, interferon-γ (IFN-γ), and tumor necrosis factor (TNF). In a cascading effect, these molecules can then lead to the release of prostaglandin E2 (PGE2) from other cells, resetting the hypothalamus to initiate fever (Figure 17.26).

Like other forms of inflammation, a fever enhances the innate immune defenses by stimulating leukocytes to kill pathogens. The rise in body temperature also may inhibit the growth of many pathogens since human pathogens are mesophiles with optimum growth occurring around 35 °C (95 °F). In addition, some studies suggest that fever may also stimulate release of iron-sequestering compounds from the liver, thereby starving out microbes that rely on iron for growth. 3

During fever , the skin may appear pale due to vasoconstriction of the blood vessels in the skin, which is mediated by the hypothalamus to divert blood flow away from extremities, minimizing the loss of heat and raising the core temperature. The hypothalamus will also stimulate shivering of muscles, another effective mechanism of generating heat and raising the core temperature.

The crisis phase occurs when the fever breaks. The hypothalamus stimulates vasodilation , resulting in a return of blood flow to the skin and a subsequent release of heat from the body. The hypothalamus also stimulates sweating, which cools the skin as the sweat evaporates.

Although a low-level fever may help an individual overcome an illness, in some instances, this immune response can be too strong, causing tissue and organ damage and, in severe cases, even death. The inflammatory response to bacterial superantigens is one scenario in which a life-threatening fever may develop. Superantigens are bacterial or viral proteins that can cause an excessive activation of T cells from the specific adaptive immune defense, as well as an excessive release of cytokines that overstimulates the inflammatory response. For example, Staphylococcus aureus and Streptococcus pyogenes are capable of producing superantigens that cause toxic shock syndrome and scarlet fever , respectively. Both of these conditions can be associated with very high, life-threatening fevers in excess of 42 °C (108 °F).

Check Your Understanding

  • Explain the difference between exogenous and endogenous pyrogens.
  • How does a fever inhibit pathogens?

Clinical Focus


Given her father’s premature death, Angela’s doctor suspects that she has hereditary angioedema , a genetic disorder that compromises the function of C1 inhibitor protein. Patients with this genetic abnormality may have occasional episodes of swelling in various parts of the body. In Angela’s case, the swelling has occurred in the respiratory tract, leading to difficulty breathing. Swelling may also occur in the gastrointestinal tract, causing abdominal cramping, diarrhea, and vomiting, or in the muscles of the face or limbs. This swelling may be nonresponsive to steroid treatment and is often misdiagnosed as an allergy.

Because there are three types of hereditary angioedema, the doctor orders a more specific blood test to look for levels of C1-INH, as well as a functional assay of Angela’s C1 inhibitors. The results suggest that Angela has type I hereditary angioedema, which accounts for 80%–85% of all cases. This form of the disorder is caused by a deficiency in C1 esterase inhibitors, the proteins that normally help suppress activation of the complement system. When these proteins are deficient or nonfunctional, overstimulation of the system can lead to production of inflammatory anaphylatoxins, which results in swelling and fluid buildup in tissues.

There is no cure for hereditary angioedema, but timely treatment with purified and concentrated C1-INH from blood donors can be effective, preventing tragic outcomes like the one suffered by Angela’s father. A number of therapeutic drugs, either currently approved or in late-stage human trials, may also be considered as options for treatment in the near future. These drugs work by inhibiting inflammatory molecules or the receptors for inflammatory molecules.

Thankfully, Angela’s condition was quickly diagnosed and treated. Although she may experience additional episodes in the future, her prognosis is good and she can expect to live a relatively normal life provided she seeks treatment at the onset of symptoms.

Immune Response

When an infection develops, the immune system also responds by producing several substances and agents that are designed to attack the specific invading microorganisms (see Acquired Immunity). Examples are

Killer T cells (a type of white blood cell) that can recognize and kill the invading microorganism

Antibodies that target the specific invading microorganism

Antibodies attach to and immobilize microorganisms. They kill them outright or help neutrophils target and kill them.

How well the immune system defends the body against each microorganism depends partly on a person's genetic make-up.

7 Signs Your Bloating Is Actually A Larger Inflammation Issue

Bloating isn't fun for anyone. It's uncomfortable, sometimes painful, and occasionally embarrassing, depending on if the bloating is obvious or noticeable. But sometimes your bloating isn't as benign or innocent as you might think, sometimes there are some signs your bloating is actually a larger inflammation issue, rather than just due to eating foods like broccoli, beans, and onions, to name just a few. If your bloating comes accompanied with other symptoms, that could be an indication that you might have more to worry about than just your belly bloat and that you need to make an appointment with your doctor.

Bloating isn't entirely uncommon, but recognizing when you're bloated, as well as if you ate or drank something that might be causing your bloating, is important in determining what kind of thing with which you might be dealing. There are some red flags that you need to know about, particularly if you find yourself frequently bloated, that it's more than belly bloat and might be something like a chronic condition, infection, or bacterial overgrowth that can be addressed, making you feel better and bloat less often. Talking to your doctor about what else is going on in your body beyond just bloating, as well as how often you're bloating and how soon after eating that you're feeling bloated can help them determine the best way to proceed.

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So, Which Fever-Fighter Is Better?

"There are no head-to-head comparisons to say one is better than the other" at reducing fevers, Dr. Kemmerly says. That includes for COVID-19 symptoms. Both acetaminophen and ibuprofen are available in tablets, capsules, solutions, melts and chewables and are easy to use, Mansukhani adds.

Ibuprofen, of course, is better if you have any kind of inflammation like rheumatoid arthritis, osteoarthritis or migraines. But it comes with more side effects.

"Some physicians will just go ahead and start with acetaminophen because of the lower risk of side effects," says Sherri Willard-Argyres, PharmD, a clinical pharmacist with MedSavvy.

Ultimately, personal preference, along with what works best with your symptoms, can drive your decision.

You can also alternate acetaminophen and ibuprofen, as long as you don't fall into a group that shouldn't use one or the other. "What we do sometimes with unrelenting temperatures, because each drug works on different receptors, is alternate for short periods of time, 24 to 48 hours max," Dr. Kemmerly says.

Watch the video: 68 Fieber vs Corona (January 2023).