Written by Josue Navarro '26
Edited by Jason Johnston '23
Human existence and survival depends on the ability to fight off disease. On an average day, we are exposed to about 60,000 types of pathogens [1]. Though most are not harmful, a few have the potential to cause disease. But, what happens when an immune system targets its own cells? Autoimmune diseases arise as a result, Rheumatoid Arthritis (RA) being one example. RA is the most common inflammatory disease, affecting 1% of the world’s population [2]. In this disease, leukocytes (white blood cells) mount an inflammatory disease which activates cytokines, inflammatory signals, and other immune cells to destroy what they perceive as invasive pathogens. By doing so, however, these immune cells target perfectly healthy cells at joints, which deteriorate over time. As a result, joint pain and swelling occurs, which can lead to bone erosion and joint deformity over time [3]. In response, researchers have developed disease-modifying antirheumatic drugs or DMARDs to treat this condition and others [4].
But what exactly induces the robust and harmful response to the body’s self that is seen in Rheumatoid Arthritis? Scientists have found many factors that contribute to RA. There is evidence to suggest that genetic predispositions and environmental factors play a role in the disease by increasing the number of antibodies targeting the body’s own proteins [2]. In RA, macrophages mount an aggressive immune response by attacking the body’s healthy cells. They are activated by cytokines (potent chemical signals in the body) and T cells. T cells are responsible for activating a specific immune response of an invading pathogen. As a result of their activation against what they perceive as a threat, they activate other immune cells (B cells, macrophages, and neutrophils) to attack the joints of the body. B cells produce antibodies which flag cells for destruction, macrophages digest pathogens, and neutrophils neutralize pathogens. When all of these cells are induced by inflammatory cytokines such as IL-6, they mount an immune response in order to defend the host [5]. However, in this instance, such a defense is harmful because healthy cells are being destroyed. But, a study conducted in 2021 by Makuch et al. found that a compound called curcumin can be used to treat rheumatoid arthritis and its symptoms [2].
The exact cause for such a reaction is still undetermined and there is no cure for this disease. However, drugs such as Rheumatrex and Trexall have been developed in order to alleviate the pain and inflammation associated with RA to prevent permanent tissue damage [6]. However, side effects of the medication include fever, chills, and low blood cell counts [7]. In 2021, Swiss medical experts from Wroclaw Medical University studied the spice curcumin—derived from turmeric—and its interactions with immune cells responsible for Rheumatoid Arthritis. They found that curcumin possesses anti-inflammatory properties [2]. These include the ability to reduce the levels of reactive oxygen species, weaken redox signaling, and reduce inflammation. In macrophages, curcumin inhibits NF-κB activation [8]. This transcription factor plays an important role in activation of an immune response and inflammation. Inhibiting this process in Rheumatoid Arthritis limits the amount of inflammation occurring at joints. In other words, curcumin prevents inflammation by blocking signals that would otherwise induce inflammation in an immune system that is attacking itself. Additionally, curcumin can reduce proinflammatory cytokine production to slow the production of immune cells. These cytokines include IL-4, IL-5, and GM-CSF. Furthermore, curcumin can increase the production of the anti-inflammatory cytokine IL-10. This cytokine is unique in that it plays a role in counteracting inflammatory conditions. Thus, the presence of more IL-10 leads to less inflammation. In addition, curcumin was found to limit the activation of neutrophils which migrate from the bloodstream into tissues (affecting the joints in this case).
Curcumin has been found to have an array of positive effects that reduce the inflammation caused by the body harming itself. Though the causes of this disease remain unknown, it is worth noting that with the right treatment, people with RA can live as long as healthy individuals [9]. Curcumin can be seen as a natural alternative to medication that reduces inflammation. Unfortunately, curcumin is not widely available and is hard to produce in the form of a tablet or capsule, which are potential downsides in using it to treat RA. Natural alternatives to treating disease is something that should be valued and taken into consideration to complement modern therapeutics.
References
1. Brownstein J, Chitale R. 10 Germy Surfaces you Touch Everyday [Internet]. ABC News. ABC News Network; 2008 [cited 2022Nov13]. Available from: https://abcnews.go.com/Health/ColdandFluNews/story?id=5727571&page=1
2. Makuch S, Więcek K, Woźniak M. The Immunomodulatory and Anti-inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis. Pharmaceuticals. 2021;14(4):309.
3. Mayo Clinic Staff. Rheumatoid Arthritis [Internet]. Mayo Clinic. Mayo Foundation for Medical Education and Research; 2021 [cited 2022Nov13]. Available from: https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648
4. Cohen S, Cannella A. Patient Education: Disease-modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis (Beyond the Basics) [Internet]. UpToDate. 2022 [cited 2022Nov13]. Available from: https://www.uptodate.com/contents/disease-modifying-antirheumatic-drugs-dmards-in-rheumatoid-arthritis-beyond-the-basics
5. Rose-John S, Winthrop K, Calabrese L. The Role of IL-6 in Host Defence against Infections: Immunobiology and Clinical Implications [Internet]. Nature News. Nature Publishing Group; 2017 [cited 2022Nov13]. Available from: https://www.nature.com/articles/nrrheum.2017.83
6. Ratini M. Rheumatoid Arthritis (RA) Treatment: Medications, Surgery, Therapy [Internet]. WebMD. WebMD; 2022 [cited 2022Nov13]. Available from: https://www.webmd.com/rheumatoid-arthritis/understanding-rheumatoid-arthritis-treatment
7. Cunha JP. Side Effects of Rheumatrex (Methotrexate Tablets), Warnings, Uses [Internet]. RxList. RxList; 2020 [cited 2022Nov13]. Available from: https://www.rxlist.com/rheumatrex-side-effects-drug-center.htm
8. Kandola A. Rheumatoid Arthritis (RA) Prognosis and Life Expectancy [Internet]. Bard S, editor. Medical News Today. MediLexicon International; 2022 [cited 2022Nov13]. Available from: https://www.medicalnewstoday.com/articles/323631
9. Park M, Hong J. Roles of NF-ΚB in cancer and inflammatory diseases and their therapeutic approaches. Cells. 2016;5(2):15.