Immunosuppressants are medications that decrease the activity of cells in your immune system. People who receive organ transplants take immunosuppressants to prevent organ rejection, which happens when the recipient’s immune system recognizes the transplanted organ as foreign tissue and attacks it.

Immunosuppressive drugs are often given to people with autoimmune diseases to help reduce immune system activity. However, immunosuppressants are potent drugs with multiple side effects ranging in severity including nausea, vomiting, diarrhea, and a heightened risk of infection.

In this article, we look at the side effects of immunosuppressants and cover common types of immunosuppressive medications, their functionality, and their use.

What Are Immunosuppressants?

Immunosuppressant drugs reduce the body’s immune response. Many immunosuppressants were first used to stop patients’ immune systems from rejecting transplanted organs and stem cells, before later being used to treat autoimmune diseases. (Source)

How Do Immunosuppressants Work?

Immunosuppressants lessen the immune response associated with autoimmune diseases by inhibiting the inflammatory cascade characteristic of the immune response. By doing so, immunosuppressive agents reduce inflammation and minimize symptoms. Immunosuppressant drugs also help restore immune tolerance towards self-antigens to reduce or stop attacks on the body’s own cells and tissues. Immunosuppressants can even put an autoimmune disease into remission. (Source, Source)

Cytokines Tell the Immune System How To Do Its Job

Cytokines (molecules that communicate between different parts of the body) play an active role in the function of your immune system. Cytokines regulate the growth and activity of immune cells, working to coordinate and mount an effective immune response. Because of their role in the immune response, cytokines are often the target of immunosuppressive drugs.

Cytokines attach to receptor cells and trigger a signaling cascade that leads to changes in gene expression in the target cell. They affect the differentiation (cell changes, often leading to their maturity), proliferation (spread), and activation of cells involved in the immune response. These actions tell the immune system to do its job. (Source, Source)

The Immune System Has Two Parts

The immune system consists of two parts: innate, which is the system you are born with, and adaptive, the system you develop over time. Two important distinctions between the innate and adaptive immune systems are reaction time and the effect of repeated exposure. The innate immune response is rapid and does not improve with repeated exposure to a pathogen. Unlike the innate immune system, the adaptive response is slow and improves with repeated exposure. (Source)

Immunosuppressants and the Innate Immune System

The innate immune system is your first line of defense against bacteria. It consists of the cells in your nose, gut, skin, and lungs. The innate immune system produces cytokines, which contribute to the immune response and participate in many other pathways in the body, notably the mechanisms involved in inflammation. Immunosuppressants acting on the innate immune system target cytokines to prevent the signaling cascade that leads to an immune response. (Source)

Immunosuppressants and the Adaptive Immune System

T-cells and B-cells, two types of white blood cells, are responsible for developing your adaptive immune system. T-cells and B-cells (which produce antibodies) recognize viruses or harmful bacteria in your body and attack these pathogens, removing the infection. The body will remember this infection so that if you become sick again, your immune system can immediately fight the pathogen. (Source)

The adaptive immune system contributes to the ability to distinguish between self and nonself antigens. With autoimmune diseases, the body cannot make this distinction, so adaptive immune cells — such as T-cells — end up tagging self-antigens for destruction. Some immunosuppressants work to inhibit T-cells, reducing the severity of an immune response and preventing T-cells from activating other immune cells. (Source, Source)

What Are the Types of Immunosuppressants?

Commonly prescribed general classes of immunosuppressants include corticosteroids, calcineurin inhibitors, and antiproliferative agents. These immunosuppressant drugs either prevent or reduce the intensity of an immune response. (Source, Source, Source)

Corticosteroids

Because they decrease inflammation and reduce immune system activity, corticosteroids are often used to treat autoimmune diseases, particularly rheumatoid arthritis and systemic lupus erythematosus (SLE). Corticosteroids block the formation of cytokines (signaling molecules involved in inflammatory and immune pathways), making it difficult for other immune and inflammatory cells to turn on and respond appropriately. By preventing the formation of cytokines, corticosteroids weaken the immune response, reduce inflammation, and mitigate symptoms associated with autoimmune diseases.

Calcineurin Inhibitors

Calcineurin inhibitors (generic names include cyclosporine and tacrolimus) act on T-cells to prevent them from producing cytokines or more T-cells. This weakens your immune system, resulting in a decreased immune response.

Antiproliferative Agents

Antiproliferative agents (generic names include mycophenolate mofetil and azathioprine) weaken the immune response by slowing down the process of producing T-cells and B-cells. In addition, antiproliferative agents influence DNA synthesis, preventing DNA from being made correctly. Without the correct DNA, T-cells and B-cells are made differently and less effectively and cannot spread as readily throughout the body. This reduces your body’s ability to mount an immune response.  

Disease-Modifying Anti-Rheumatic Drugs

Disease-modifying anti-rheumatic drugs (DMARDs) are immunosuppressive and immunomodulatory, meaning they weaken and change your immune response. Some DMARDs target the immune system broadly, while others act on specific inflammatory pathways. DMARDs treat joint pain, swelling, and arthritis that often accompany autoimmune disease. Because of this, DMARDs are frequently used with rheumatoid arthritis, where they have been found to slow disease progression and preserve joints. (Source, Source, Source)

Side Effects of Immunosuppressants

Despite the benefits of immunosuppressants in treating autoimmune diseases, these medications are not without risks and side effects. By reducing your immune response, immunosuppressive agents weaken your body’s ability to fight off other infections and diseases.

A serious side effect of immunosuppressants is your increased risk of infection, specifically blood, fungal, skin, or respiratory infections. The risk of infection depends on your autoimmune disease and the specific immunosuppressant you may be taking. Increased risk of cancer is another long-term complication of immunosuppressants. (Source)

Because immunosuppressants reduce your ability to fight infections, it’s important to consult your health care provider immediately if you experience fever, chills, flu-like symptoms, or have a cough or cold you can’t shake. Keep in mind, though, that because these drugs reduce immune response you can have an infection without noticing typical symptoms of illness, so check in with your provider if you feel off in any way. (Source)

Side effects differ depending on the immunosuppressant. Some of the more common side effects of immunosuppressants include:

• hyperglycemia (high blood sugar) and onset of type 2 diabetes
• hyperlipidemia (high levels of “bad” cholesterol and low levels of “good” cholesterol)
• insomnia
• gastrointestinal issues such as diarrhea, nausea, vomiting, and abdominal pain
• irritability, mood changes, and depression
• headaches
• bone loss (osteoporosis)
• fatigue
• weight gain
• skin rashes
• tremors

(Source, Source)

Biologic Therapies Versus Immunosuppressants

Biologics, medications that are administered intravenously rather than orally, target specific pathways in the immune response. Specifically, biologics weaken the actions of cytokines involved in your innate or adaptive immune responses. Biological therapies may be used as an alternative to immunosuppressive drugs and may be prescribed when disease-modifying anti-rheumatic drugs are unsuccessful. (Source, Source)

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Biologic therapies are not without their own side effects, some of which (such as gastrointestinal distress, headaches, and changes in blood pressure) resemble side effects associated with immunosuppressants. And as with immunosuppressive agents, possible complications of biologics include infections. (Source)

Comprehensive Care Can Help Manage Side Effects

The autoimmune protocol (AIP) diet, which emphasizes whole and anti-inflammatory foods, can help manage some side effects of immunosuppressants. Lifestyle modifications may aid with managing hyperglycemia (high blood sugar levels) and hyperlipidemia (high cholesterol levels), two side effects often associated with corticosteroids. Try limiting sugar and refined grains. Instead, consider choosing whole foods rich in fiber and healthy organic fats that contribute to regulating blood sugar and lipid levels. Our Nutritional Therapy Practitioners can work with you to find lifestyle and dietary modifications to alleviate some of your medication side effects.

Take Steps to Lower Your Risk of Infection

Infection is the most serious complication that can result from taking immunosuppressants. Because your immune response is reduced, you are at a heightened risk of contracting an infection. However, you can take steps to lower your chance of getting an infection.

Practice Thorough Hand-Washing

Washing your hands frequently and thoroughly with soap and water is one of the most important steps for reducing your infection risk. Make sure to wash your hands before eating or preparing food and after touching anything that may have been in contact with feces, human or animal. (Source)

Reduce Exposure to Contaminants in Food and Water

Wash or cook fresh fruits and vegetables to limit the risk of exposure to harmful contaminants such as bacteria. Ensure that the water you drink is safe; if not, boil your water, install a water filter, or choose bottled water. (Source)

Prevent Infection

Limit contact with people who are sick, and stay home if you feel unwell. If you have to cough or sneeze, do so into a tissue or your elbow, then wash your hands. Clean and disinfect surfaces that are frequently touched. Staying current with your vaccinations, especially flu and pneumonia, can also help protect you from a respiratory infection; talk to your medical provider about this. (Source, Source)

Get Adequate Sleep

Sleep has a significant effect on immune pathways. Inadequate sleep can contribute to immune system dysregulation and inflammation, both of which can increase the possibility of infection. Individuals who sleep less than 5 hours may be more susceptible to respiratory infections. Likewise, short sleep duration is associated with an increased risk of common illnesses, such as colds and the flu. Aiming for 7 to 8 hours of sleep may help reduce your risk of infection. (Source)

The Bottom Line on Side Effects of Immunosuppressants

Immunosuppressants can reduce symptoms of autoimmune disease and even put some conditions into remission, but their use does come with a price. Don’t be discouraged if you experience side effects of your immunosuppressive medication; finding the right treatment plan can be difficult. Your health care provider will work with you to determine which immunosuppressive drug is best for you and will support you through any side effects. In addition, the team at WellTheory is here to help you navigate and manage life with autoimmunity, through simple and personalized nutrition and lifestyle changes that can fit into any preexisting care plan you may have.

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