Ivermectin and its many uses
Although ivermectin is best known as an antiparasitic medication (read all about “repurposed medications” [HERE]), researchers have also identified a number of anti-inflammatory and immunomodulatory effects. These effects occur through several interconnected signalling pathways that regulate how immune cells respond to potential threats.
One of the most important pathways involves a protein called NF-κB, which acts as a central regulator of inflammation. When the immune system detects certain danger signals, including components of bacteria such as lipopolysaccharide (LPS), receptors like TLR4 can activate NF-κB. Once activated, NF-κB enters the cell nucleus and stimulates the production of inflammatory substances, including cytokines such as TNF-α, IL-1β and IL-6.
Research also shows that ivermectin can interfere with this signalling process by reducing TLR4-related signalling and inhibit activation of NF-κB, which can subsequently decrease the production of several inflammatory cytokines. In this way, ivermectin reduces the intensity of the inflammatory response rather than simply blocking a single inflammatory molecule.
Ivermectin also influences another group of signalling pathways known as MAPK pathways, including JNK and p38. These pathways help cells respond to stress and inflammatory stimuli. Studies have found that ivermectin reduces activation of these pathways, providing another mechanism through which it limits inflammatory signalling.
Another area of interest is STAT3, a protein involved in immune regulation and inflammation. Excessive STAT3 activation, particularly in response to IL-6, can contribute to prolonged inflammatory signalling. Studies suggest that ivermectin can interfere with the PAK1/STAT3/IL-6 pathway, reducing the production of IL-6 and other inflammatory mediators.
Ivermectin also affects the behaviour of macrophages – immune cells that play an important role in initiating and regulating inflammation. When macrophages become excessively activated, they can release large amounts of inflammatory cytokines and other substances that perpetuate tissue inflammation.
There is also evidence that ivermectin interacts with P2X receptors, which respond to extracellular ATP (ATP normally functions as an energy source within cells, but when cells are injured or under significant stress, ATP can be released into the surrounding tissue and act as a danger signal). By influencing these receptors, ivermectin affects another mechanism involved in regulating immune and inflammatory responses.
Taken together, these findings show that ivermectin has immunomodulatory rather than simply immunosuppressive properties. Its anti-inflammatory activity involves several levels of the inflammatory signalling network, including TLR4, NF-κB, MAPK and STAT3 pathways, as well as the activity of immune cells such as macrophages.
What kind of conditions can ivermectin treat?
There are quite a few diseases involving inflammatory pathways that ivermectin has been shown to modulate, including the following:
1. Neuroinflammatory diseases, such as:
– multiple sclerosis
– neurodegeneratiev diseases
– certain forms of encephalitis
– traumatic brain injury
The reason ivermectin works here is that some of the pathways it influences, particularly TLR4, NF-κB, MAPK and inflammatory cytokine signalling, are also involved in activation of microglia and neuroinflammatory responses.
2. Autoimmune and inflammatory diseases, like:
– rheumatiid arthritis
– inflammatory bowel disease
– psoriasis
– lupus
– certain forms of inflammatory arthritis
This is because pathways such as NF-κB, MAPK and STAT3 participate in inflammatory signalling across many of these diseases.
3. Inflammatory skin diseases
Ivermectin is already used topically for papulopustular rosacea, where its effects involve both elimination of Demodex mites and reduction of inflammatory signalling. Other examples it treats include:
– atopic dermatitis (eczema)
– seborrhoeic dermatitis
– acne vulgaris
– allergic contact dermatitis
– cutaneous lupus, and others
4. Respiratory and allergic inflammation
This is another area where the biology is interesting, particularly because NF-κB and MAPK signalling are important in airway inflammation; examples include:
– asthma (including allergic asthma)
– allergic rhinitis (hay fever)
– chronic obstructive pulmonary disease (COPD)
– Eosinophilic bronchitis
– occupational asthma
– atopic cough
– nasal polyps (particularly when associated with type 2 inflammation)
5. Cancer-associated inflammation
Chronic inflammation can contribute to cancer in several ways; persistent inflammatory signalling can cause oxidative and DNA damage, stimulate cell proliferation, promote the formation of new blood vessels and alter the surrounding tissue in ways that can support tumour growth. Inflammatory cytokines such as IL-6 and TNF-α, along with signalling pathways including NF-κB and STAT3, can influence tumour-cell survival, proliferation, invasion and resistance to cell death.
Inflammation can also affect the tumour microenvironment, which consists of the immune cells, blood vessels, connective tissue and signalling molecules surrounding a tumour. Rather than simply being a passive environment, these surrounding cells can release cytokines and growth factors that influence how a tumour behaves. In some circumstances, cancer cells can also exploit inflammatory signalling to evade immune surveillance and create conditions that favour their survival.
Because ivermectin influences several pathways involved in inflammation, including NF-κB, STAT3 and PAK1 signalling, ivermectin is an excellent candidate for drug-repurposing research in oncology.
Ivermectin has an effect on a number of cancer-related processes, including cancer-cell proliferation, apoptosis, oxidative stress and signalling pathways involved in tumour survival.
Ivermectin is a safe, long-discovered, naturally-derived repurposed medication that many people are seeing relief by using. For further questions, please refer to your healthcare practitioner to ensure it is right for your use, or contact us with your questions.
Sources:
Zhang et al., 2008 – primary evidence for NF-κB and inflammatory cytokines. https://pubmed.ncbi.nlm.nih.gov/19109745/
Ci et al., 2009 – primary evidence for NF-κB, JNK and p38/MAPK. https://pubmed.ncbi.nlm.nih.gov/19453757/
Dou et al., 2019 – primary evidence for PAK1/STAT3/IL-6. https://pubmed.ncbi.nlm.nih.gov/31658701/
Khan et al., 2021 – useful review tying the mechanisms together and explaining the proposed TLR4/NF-κB/MAPK relationship. https://www.nature.com/articles/s41429-021-00491-6
https://pubmed.ncbi.nlm.nih.gov/40220854
https://www.nature.com/articles/s41429-020-0336-z
https://www.sciencedirect.com/science/article/pii/S022352342300805X
