Inflammation as a Cause of Disease

Image Credit: Marco Verch (Flickr)

What is Inflammation? Two Immunologists Explain How the Body Responds to Everything from Stings to Vaccination and Why it Sometimes Goes Wrong

When your body fights off an infection, you develop a fever. If you have arthritis, your joints will hurt. If a bee stings your hand, your hand will swell up and become stiff. These are all manifestations of inflammation occurring in the body.

We are two immunologists who study how the immune system reacts during infections, vaccination and autoimmune diseases where the body starts attacking itself.

This article was republished with permission from The Conversation, a news site dedicated to sharing ideas from academic experts. It represents the research-based findings and thoughts of Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South Carolina and Mitzi Nagarkatti Professor of Pathology, Microbiology and Immunology, University of South Carolina

While inflammation is commonly associated with the pain of an injury or the many diseases it can cause, it is an important part of the normal immune response. The problems arise when this normally helpful function overreacts or overstays its welcome.

What is Inflammation?

Generally speaking, the term inflammation refers to all activities of the immune system that occur where the body is trying to fight off potential or real infections, clear toxic molecules or recover from physical injury. There are five classic physical signs of acute inflammation: heat, pain, redness, swelling and loss of function. Low-grade inflammation might not even produce noticeable symptoms, but the underlying cellular process is the same.

Take a bee sting, for example. The immune system is like a military unit with a wide range of tools in its arsenal. After sensing the toxins, bacteria and physical damage from the sting, the immune system deploys various types of immune cells to the site of the sting. These include T cells, B cells, macrophages and neutrophils, among other cells.

The B cells produce antibodies. Those antibodies can kill any bacteria in the wound and neutralize toxins from the sting. Macrophages and neutrophils engulf bacteria and destroy them. T cells don’t produce antibodies, but kill any virus-infected cell to prevent viral spread.

Additionally, these immune cells produce hundreds of types of molecules called cytokines – otherwise known as mediators – that help fight threats and repair harm to the body. But just like in a military attack, inflammation comes with collateral damage.

The mediators that help kill bacteria also kill some healthy cells. Other similar mediating molecules cause blood vessels to leak, leading to accumulation of fluid and influx of more immune cells.

This collateral damage is the reason you develop swelling, redness and pain around a bee sting or after getting a flu shot. Once the immune system clears an infection or foreign invader – whether the toxin in a bee sting or a chemical from the environment – different parts of the inflammatory response take over and help repair the damaged tissue.

After a few days, your body will neutralize the poison from the sting, eliminate any bacteria that got inside and heal any tissue that was harmed.

Asthma is caused by inflammation that leads to swelling and a narrowing of airways in the lungs, as seen in the right cutaway in this image. BruceBlaus/Wikimedia Commons, CC BY-SA

Inflammation as a Cause of Disease

Inflammation is a double-edged sword. It is critical for fighting infections and repairing damaged tissue, but when inflammation occurs for the wrong reasons or becomes chronic, the damage it causes can be harmful.

Allergies, for example, develop when the immune system mistakenly recognizes innocuous substances – like peanuts or pollen – as dangerous. The harm can be minor, like itchy skin, or dangerous if someone’s throat closes up.

Chronic inflammation damages tissues over time and can lead to many noninfectious clinical disorders, including cardiovascular diseases, neurodegenerative disorders, obesity, diabetes and some types of cancers.

The immune system can sometimes mistake one’s own organs and tissues for invaders, leading to inflammation throughout the body or in specific areas. This self-targeted inflammation is what causes the symptoms of autoimmune diseases such as lupus and arthritis.

Another cause of chronic inflammation that researchers like us are currently studying is defects in the mechanisms that curtail inflammation after the body clears an infection.

While inflammation mostly plays out at a cellular level in the body, it is far from a simple mechanism that happens in isolation. Stress, diet and nutrition, as well as genetic and environmental factors, have all been shown to regulate inflammation in some way.

There is still a lot to be learned about what leads to harmful forms of inflammation, but a healthy diet and avoiding stress can go a long way toward helping maintain the delicate balance between a strong immune response and harmful chronic inflammation.

The Biotech Field That’s Getting Big Pharma’s Attention at the Earliest Stages

Image Credit: Ed Schipul (Flickr)

Small Biotech Field with Big Promise

A silver bullet cure, with possible indications for 150 illnesses or more, is now being researched by a few small biotech companies. The results have gotten the attention of big pharmaceutical companies.

In the world of biology, medicine, and biotechnology, there’s a new and extremely promising field of research in inflammasomes. Since the discovery 20 years ago, increasing understanding of what causes inflammation or an inflammatory response in humans and the knowledge of the mechanisms and role of inflammasomes has developed into a race to design potential drugs which target the culprit in many diseases. The problem to be solved is an overly zealous inflammatory response.

The activation of the inflammation system is to protect the body from pathogens, injury, or other dangers or irritants. While insufficient inflammation can lead to persistent infection or problems related to the initial trigger, excessive inflammation can cause chronic or systemic inflammatory diseases. While there are many medications, both over-the-counter and by prescription, to help reduce inflammation and problems associated with it, a therapy or therapies upstream could prevent an over-inflammation response at the source.

Currently, the rapid expansion of knowledge of inflammasomes’ role in various diseases has uncovered links to neurological diseases such as Parkinson’s, Alzheimer’s, and MS; metabolic disorders including type2 diabetes, and obesity; and cardiovascular diseases.

Currently, there are no approved inflammasome inhibitors; however, there are several promising early-stage trials occurring at a few focused companies. Development of therapies is the goal, with expectations of them being able to treat a myriad of ailments. Success could be similar to the discovery of penicillin when many infections quickly ceased being worrisome. The breakthrough could provide therapy or a mechanism to control one or two key inflammasomes that could suddenly provide cures or relief from many chronic problems.

Over the past few years, these inflammasome-related transactions, acquisitions, and partnerships have taken place:

Ventus Therapeutics- On September 29, 2022, Ventus received $70 million upfront, with the agreement for additional milestones of up to $633 million, also royalty payments and R&D funding from Novo Nordisk to license Ventus’s brain penetrant inflammasome (NLRP3) inhibitor – Ventus is a privately held company that retains full rights.

Cerevance – August 9, 2022 Cerevance received $25 million upfront, with the agreement for additional milestones up to $1.1 billion, with potential for royalty payments from Merck on sales of approved products derived from the strategic research collaboration of Alzheimer’s targets using Cerevance’s NetSseq platform. (Pre-clinical phase)

Inflamazome – September 21, 2020 Inflamazome was fully acquired for $451 million upfront with R&D milestones that could be worth up to $1.125 billion from Roche. Roche will own full rights to the acquired company’s portfolio of oral NLRP3 small molecule inflammasome inhibitors. (Pre-clinical phase and Phase 1)

IFM Therapeutics – Quattro & IFM Discovery (Incubator) – December 2019, Has raised $55.5 million to launch its third drug subsidiary as well as an incubator, both of which are focused on developing new therapies for inflammatory diseases and cancers. Omega Funds was the lead, with Atlas Ventures also participating. Financing lead: Omega Funds also participating: Atlas Ventures. (Discovery Phase)

Inflammasome Therapeutics – September 2019,  Is entitled to receive up to $160 million in milestone and gated development payments and tiered royalties and other milestones due on commercialization from Boehringer Ingelheim. (Development Phase)

IFM Therapeutics – September 2019, Agreement provides sufficient funding for research and development costs through late-stage pre-clinical development of the lead program with an option to acquire IFM Due. IFM is a Privately held company. (Discovery Phase)

IFM Therapeutics- April 1, 2019, the subsidiary IFM Tre was acquired by Novartis. Novartis will pay $310 million upfront and up to roughly $1.3 billion in milestones to access three early-stage NLRP3 antagonists: IFM-2427, a systemically acting compound that began its first human studies last week, and two pre-clinical compounds: one gut-penetrating, and the other directed at the central nervous system. (Clinical Phase and Pre-clinical Phases)

Most of the small companies involved in inflammasome research are privately held and raise capital privately. From time to time, Noble Capital Markets may be involved in raising capital for non-public biotech firms and companies in other industries. To determine in advance if you qualify to invest in non-public capital raises, visit here to request accreditation.

Take Away

There are huge amounts of capital coming primarily from big pharma and venture capital firms with the expectation that R&D on inflammasomes could yield big results. Therapies that could regulate a primary culprit across many diseases would be a significant boost to investors and mankind.

Paul Hoffman

Managing Editor, Channelchek

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