HomeENGLISH MAGAZINEDrug side effects in autoimmunity: focus now is laid onto cellular fat...

Drug side effects in autoimmunity: focus now is laid onto cellular fat metabolism

Autoimmune rheumatic diseases or AIRD affect millions of people around the world and include rheumatoid arthritis, lupus and Sjögren’s syndrome, all of which have high rates of morbidity. They occur when the immune system mistakenly attacks and damages its own tissues, although the pathogenesis (the mechanism that triggers it) is still poorly defined and providing targeted therapeutic strategies is difficult. As a result, current treatments for AIRDs are primarily designed to suppress symptoms (inflammation), but are “low target,” which means drugs can also have unintended side effects. In this regard, drugs often cause changes in cellular metabolism and function, exposing patients to a greater risk of co-morbidities such as cardiovascular disease. A new large-scale review led by UCL researchers has now found that new AIRD therapies designed to better regulate fat metabolism could significantly reduce the harmful side effects caused by conventional treatments.

For the study, published in the Journal of Clinical Investigation, the researchers performed a literature review of more than 200 studies to evaluate and interpret what is known about on-target / off-target (adverse) effects and mechanisms of action of current AIRD therapies on lipid metabolism, immune cell function and cardiovascular risk. Well, the data found that current therapies can both improve and worsen lipid metabolism, and one of these changes could cause inflammation and an increased risk of CVD. Many conventional drugs also require cellular metabolism for their conversion into therapeutically beneficial products; however, drug metabolism often results in the additional formation of toxic byproducts, and drug metabolism rates may differ between patients. The review found that better inflammation control using optimal combinations of immunosuppressive treatments could lead to a better metabolic / lipid profile in affected patients.

However, it also revealed that many studies have shown that lipid-lowering drugs (such as statins) are not sufficient to reduce cardiovascular risk in some autoimmune diseases, potentially because they cannot fully restore anti-inflammatory properties. Referring to other drugs, for example cortisone, it is known that these have a strong deteriorating effect on the metabolism of carbohydrates and fats. Their chronic use is notoriously associated with overweight and secondary obesity induced by their own intake. Other immunoregulators such as hydroxychloroquine (the well-known Plaquenil) greatly influence liver function over time, being able to induce an increase in transaminases and the appearance of steatosis (fatty liver). The other classic immunosuppressant, methotrexate (Reumaflex), in addition to damaging the bone marrow (anemia), strongly disturbs the metabolism of the liver and kidneys. Finally, leflunomide (Arava), is already a priori not used in case of existing liver problems, low blood potassium values ​​and diabetes.

In this regard, Dr George Robinson of University College London, lead author of the study, commented: “Although the mechanisms that cause rheumatic diseases are poorly defined, some recent research indicates that cellular metabolism may play an important role. triggering or worsening their onset or influence. In this review we therefore sought to understand the effect of conventional and emerging therapies on lipid metabolism in patients with AIRD. The unfavorable off-target adverse effects of current therapies offer an opportunity for optimal combinations co-therapies targeting lipid metabolism, which could reduce immune complications and the potential increased cardiovascular risk in patients. New therapeutic technologies and research have also highlighted alternative metabolic pathways that can be more specifically targeted to reduce inflammation, but also to prevent a consequence and off-target metabolics of conventional anti-inflammatory drugs. Science is working towards this”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

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Scientific references

Robinson G et al. J Clin Invest 2022; 132(2):e148552.

Cao F et al. Pharmacol Res. 2020 Oct; 160:105054.

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Dott. Gianfrancesco Cormaci

Medico Chirurgo, Specialista; PhD. a CoFood s.r.l.
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento enzimaticamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (Leader of the R&D for the partnership CoFood s.r.l.) - Autore di articoli su informazione medica e salute sul sito www.medicomunicare.it (Medical/health information on website) - Autore di corsi ECM FAD pubblicizzati sul sito www.salutesicilia.it
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