Cytokine Storms: What happens when the immune system overreacts?

This article describes an account of a hyper activated immune response known as a cytokine storm. It contains infections and diseases implicated in cytokine storms such as SARS-CoV-2, influenza, immunotherapy and rheumatoid arthritis. Pathways such as JAK-STAT, MAPK and NF-kB are detailed in relation to cytokine storms.

A cytokine is a protein that is secreted by cells of the immune system. These proteins help to regulate the immune response, and can be either pro-inflammatory or anti-inflammatory. Cytokine storms are a type of immune response that can occur when the body overreacts to an infection or other threat. This overreaction can cause widespread inflammation and tissue damage, and in severe cases, can be life-threatening. Cytokine storms are a hyper immune response most commonly seen in people with severe infections, such as sepsis, COVID-19 or influenza, but can also occur in people with certain autoimmune disorders or after receiving a vaccine. Treatment for cytokine storms typically involves using drugs to suppress the immune system. In severe cases, patients may need to be hospitalized and receive supportive care, such as oxygen therapy and IV fluids. Cytokine storms are a serious complication, but with prompt treatment, most people recover fully. The symptoms of a cytokine storm include fever, chills, rash, shortness of breath, and organ failure. Cytokine storms can occur very suddenly, and often progress rapidly. In severe cases, patients may go into shock and require hospitalization. Treatment for a cytokine storm typically involves using drugs to suppress the immune system. Corticosteroids, such as prednisone, are often used to reduce inflammation. cyclosporine and etoposide are also sometimes used to treat cytokine storms. Cytokine storms can occur in people of any age, but are most common in young children and older adults. People with certain medical conditions, such as cancer, autoimmune diseases, and chronic infections, are also at increased risk.

There are a number of different types of cytokines which include interferon (IFN), interleukin (IL), and tumor necrosis factor (TNF). Cytokines can be either pro-inflammatory or anti-inflammatory. Pro-inflammatory cytokines are involved in the body's initial response to infection or injury, and help to activate the immune system. Anti-inflammatory cytokines help to reduce inflammation once the initial response is over. IL-6 and TNF-alpha are examples of pro-inflammatory cytokines, while IL-10 and TGF-beta are examples of anti-inflammatory cytokines, interferon beta 1b is a type of interferon that is used to treat multiple sclerosis. It works by reducing the activity of the immune system. Interferon beta 1b is given as an injection under the skin or into a muscle. The usual dose is 0.25 mg once a day for 7 days, followed by 0.5 mg once a week for 4 weeks, then 1 mg once a week indefinitely. Side effects of interferon beta 1b include flu-like symptoms, such as fever, chills, muscle aches, and fatigue. These side effects usually go away after the first few doses.

Pathways implicated in cytokine storms include the JAK-STAT, MAPK, and NF-kB signaling pathways. These pathways are involved in the body's response to infection or injury, and help to regulate the immune system. Cytokine storms can occur when these pathways are activated inappropriately or become dysregulated. This can happen due to a genetic mutation, an infection, or another trigger. Cytokine storms are a type of immune response that can occur when the body overreacts to an infection or other threat. This overreaction can cause widespread inflammation and tissue damage, and in severe cases, can be life-threatening. JAK-STAT pathway is a signaling pathway that is involved in the body's response to infection or injury. The pathway is activated when a cytokine binds to its receptor on the surface of a cell. This activates the JAK kinases, which then phosphorylate the STAT proteins. The STAT proteins then translocate to the nucleus and regulate gene expression. The MAPK pathway is a signaling pathway that is involved in the body's response to infection or injury. The pathway is activated when a cytokine binds to its receptor on the surface of a cell. This activates the MAPK kinases, which then phosphorylate and activate transcription factors. The transcription factors then regulate gene expression. The NF-kB pathway is a signaling pathway that is involved in the body's response to infection or injury. The pathway is activated when a cytokine binds to its receptor on the surface of a cell. This activates the IKK complex, which then phosphorylates the NF-kB proteins. The NF-kB proteins then translocate to the nucleus and regulate gene expression.

The immune system is essential for protecting the body against infection and disease. However, when it is not working properly, it can cause a range of disorders. Autoimmune diseases are conditions in which the immune system attacks healthy tissue by mistake. Common autoimmune diseases include rheumatoid arthritis, psoriasis, and multiple sclerosis. Infections, such as HIV and tuberculosis, can also weaken the immune system. Cancer can also affect the immune system, either directly or indirectly. Cancer cells can release cytokines that suppress the immune response, or cancer treatments, such as radiation therapy and chemotherapy, can damage healthy cells and reduce the body's ability to fight off infection. Chronic stress can also lead to problems with the immune system.

Cytokine storms can happen in various cancers such as leukemia and lymphoma. These are types of blood cancer that start in the bone marrow and lymph nodes, respectively. Treatment for leukemia and lymphoma typically involves using drugs to suppress the immune system, such as corticosteroids, cyclosporine, and methotrexate.

Patients receiving immunotherapies such as CAR-T therapy are at risk for developing cytokine storms. CAR-T therapy is a type of immunotherapy that uses genetically engineered T cells to attack cancer cells. These therapies work by stimulating the immune system to attack cancer cells. While they can be very effective, they can also cause the immune system to overreact and produce too many cytokines. This can lead to a cytokine storm. Symptoms of a CAR-T-related cytokine storm typically begin within 2 weeks of receiving treatment. They may include fever, chills, rash, shortness of breath, and organ failure. Treatment for a CAR-T-related cytokine storm typically involves using drugs to suppress the immune system, such as corticosteroids and cyclosporine.

Those with severe infections such as sepsis or Sars-CoV-2 infection (the virus that causes COVID-19) are also at risk for developing cytokine storms. Symptoms of a sepsis-related cytokine storm typically begin within 3 days of infection. They may include fever, chills, low blood pressure, and organ failure. COVID-19 can also cause a cytokine storm. Symptoms of a COVID-19-related cytokine storm typically begin within 2 weeks of infection. They may include fever, chills, shortness of breath, and organ failure.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, inherited disorder that can also lead to cytokine storms. FHL is caused by a mutation in a gene that helps regulate the immune system. This can cause the immune system to overreact and produce too many cytokines. Symptoms of an FHL-related cytokine storm typically begin in early childhood. They may include fever, rash, and organ failure. Treatment for an FHL-related cytokine storm typically involves using drugs to suppress the immune system, such as corticosteroids and cyclosporine.

Systemic lupus erythematosus (SLE) is another autoimmune disorder that can lead to cytokine storms. SLE is caused by a combination of genetic and environmental factors. This can cause the immune system to attack healthy tissue, leading to inflammation and pain. Symptoms of an SLE-related cytokine storm typically begin in early adulthood. They may include fever, rash, and organ failure. Treatment for an SLE-related cytokine storm typically involves using drugs to suppress the immune system, such as corticosteroids, methotrexate, and hydroxychloroquine.