Inflammation, NSAIDs, Painkillers, Immunity system



Inflammation is the reaction of a part of the body to injury or infection, characterized by swelling, heat, redness, and pain. The process includes increased blood flow with an influx of white blood cells and other chemical substances that facilitate healing.
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, EC 1.14.99.1) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prostacyclin.
The prostaglandins (PG) are a group of physiologically active lipid compounds having diverse hormone-like effects in animals.
Q:

Why does your body temperature rise when you have the flu?


A: "Your body temperature rises when you have the flu as a way of fighting off the influenza virus; viruses thrive best at 98.6 degrees Fahrenheit—normal body temperature. When your body is hotter it's harder for the flu virus to survive. A fever also stimulates your immune system to fight off the illness. Although you may not feel great when you have a fever, the fever itself is helping you get better." - Stacy Wiegman, PhD, Pharmacy
A: "When the body temperature rises because of an infection, it's called fever. Fevers are caused by chemicals in the bloodstream called pyrogens. Pyrogens make their way to the brain's hypothalamus, which is in charge of regulating body temperature. When those pyrogens bind to certain receptors in the hypothalamus, the body temperature rises.
One common pyrogen is Interleukin-1 (also called IL-1). IL-1 is produced by white blood cells that are called macrophages when they connect with certain bacteria and viruses. IL-1 has multiple purposes. An important purpose is to signal white blood cells, called helper T cells, into action.
Doctors think one reason for a fever is to raise the body's temperature enough to kill off bacteria and viruses that are sensitive to temperature changes. In debate right now is whether we should be trying to lower fevers. Aspirin, for example, will reduce fever. Still, if the fever is helping rid the body of infection, then lowering it could be counterproductive. On the other hand, people sometimes die from fever. The general medical consensus right now leans to the "reduce the fever" side of the fence." - Discovery Health
Pyrogen: a substance, typically produced by a bacterium, that produces fever when introduced or released into the blood.


COX-2 Inhibitors

What are NSAIDs and how do they work?

As the class name suggests, nonsteroidal antiinflammatory drugs (NSAIDs) reduce inflammation but are not related to steroids which also reduce inflammation. NSAIDs work by reducing the production of prostaglandins. Prostaglandins are chemicals that promote inflammation, pain, and fever. They also protect the lining of the stomach and intestines from the damaging effects of acid, promote blood clotting by activating blood platelets, and promote normal function of the kidneys. Prostaglandins improve blood flow to kidneys and thus preventing kidney ischemia.

The enzymes that produce prostaglandins are called cyclooxygenases (COX). There are two types of COX enzymes, COX-1 and COX-2. Both enzymes produce prostaglandins that promote inflammation, pain, and fever; however, only COX-1 produces prostaglandins that activate platelets and protect the stomach and intestinal lining.

NSAIDs block COX enzymes and reduce production of prostaglandins. Therefore, inflammation, pain, and fever are reduced. Since the prostaglandins that protect the stomach and promote blood clotting also are reduced, NSAIDs that block both COX-1 and COX-2 can cause ulcers in the stomach and intestines, and increase the risk of bleeding.

For what conditions are NSAIDs used?

NSAIDs are used for treating conditions that cause inflammation, mild to moderate pain, and fever. Examples include:

headaches,

coughs and colds,

sports injuries,

arthritis, and

menstrual cramps.

Ketorolac (Toradol) is only used for short-term treatment of severe pain that usually requires opioid treatment.

Aspirin is the only NSAID that is used for preventing strokes and heart attacks in individuals at high risk for such events.

Discussion upon weakening immunity by NSAIDs

The NSAIDs, including Cox-2 selective inhibitors, are commonly used in the treatment of acute inflammation, chronic pain and arthritis. More recent benefits have been investigated, including the use of these drugs to delay the onset of Alzheimer’s disease and as supplements for cancer chemotherapy.14,20,21Although interest in using NSAIDs for new therapies is expanding, relatively little is known about how these drugs influence the human immune system. We provide new evidence that NSAIDs, through the inhibition of Cox-2, blunt B-cell antibody production. Our results reveal a novel mechanism for attenuated antibody production whereby Cox-2 activity is essential for the terminal differentiation of B lymphocytes. These findings implicate that the use of NSAIDs that inhibit Cox-2 dampen humoral immune responses.


HOW PARACETAMOL AND IBUPROFEN WORK 

Paracetamol and ibuprofen are two of the most common painkillers.
The two drugs work in different, but complementary ways.
Ibuprofen blocks the production of various chemicals in the body.
These include prostaglandins, which are produced in response to injury or disease and cause inflammation. 
Ibuprofen taken as pills or in liquid form numbs the site of pain and reduces inflammation, and is widely used for arthritic pain.
It has a relatively low level of side effects, although it can cause stomach bleeding, kidney damage, allergic reactions. 
It should not be taken by people who are allergic to aspirin.
Paracetamol also blocks prostaglandin, but only in the brain and spinal cord.
It reduces temperature by acting on the area of the brain responsible for controlling temperature.
Side effects are rare but can include a rash or swelling. 
Dr Smith said: ‘Medically, I’d rather someone dampened the pain, while making sure they drink enough water, staying at home in bed.''Then you are giving the body a better chance of destroying the virus
'If you drink enough and rest enough, and take paracetamol, you give your body the best chance of overcoming it.’

A local anaesthetic spray also helps with a sore throat and difficulty swallowing, without affecting the body’s immune response, he added.‘A local anaesthetic spray, doers the same, it just dampens the nasty feeling of a sore throat,’ Dr Smith said. ‘You dampen the pain locally without flooding the whole body.

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