Atorvastatin Attenuates the Expression of Damage-associated Molecular Patterns and Inflammatory Cytokines in Patients with Psoriasis

Overview

Journal Pharmacol Rep

Specialty Pharmacology

Date 2025 Mar 14

PMID 40085417

Authors

Kalliopi Armyra

Amin M Ektesabi

James N Tsoporis

Shehla Izhar

Andreas S Triantafyllis

Howard Leong-Poi

Thomas G Parker

Alexandros C Katoulis

Loukianos S Rallidis

Panagiotis G Stavropoulos

Christina Antoniou

Claudia C Dos Santos

Ioannis Rizos

Affiliations

Soon will be listed here.

Abstract

Background: In psoriasis, damage-associated molecular patterns (DAMPs) released by damaged local tissue act as danger signals and trigger inflammatory responses. Statins, in addition to cholesterol-lowering, have anti-inflammatory effects. We sought to assess the effectiveness of atorvastatin in attenuating plasma DAMPs and inflammatory cytokines in adults with psoriasis.

Methods: In this prospective 3-month study, we included 21 eligible psoriatic patients who received oral atorvastatin 10 mg/day and 14 non-psoriatic controls. Blood samples for DAMPs measurement were collected at baseline and 3 months. Additionally, efficacy outcomes were estimated using psoriasis severity index and dermatology-specific quality of life index scores at baseline and 3 months.

Results: Compared to control, psoriatic plasma showed a decrease in the decoy of DAMPs, the soluble (s) receptor for advanced glycation end products (sRAGE), and increases in the DAMPs S100B, S100A7, S1100A12, S100A8/A9, DJ-1, the inflammatory cytokines IL-6, IL-1β and TNF-α. Atorvastatin for 3 months improved efficacy scores, increased sRAGE, and decreased DAMPs and inflammatory cytokines toward control levels. Mechanistically, in the immortalized embryonic fibroblast Swiss mouse cell line NIH3T3s, S100A12, and S100A7 induced an inflammatory response and atorvastatin increased sRAGE in the medium.

Conclusion: Statin therapy is effective in lowering DAMPs-induced inflammation in psoriasis patients. The main limitation of our study is the small sample size, and the findings should be confirmed in a larger cohort.

References

Griffiths C, Barker J . Pathogenesis and clinical features of psoriasis. Lancet. 2007; 370(9583):263-271. DOI: 10.1016/S0140-6736(07)61128-3. View

Rendon A, Schakel K . Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019; 20(6). PMC: 6471628. DOI: 10.3390/ijms20061475. View

Georgescu S, Tampa M, Caruntu C, Sarbu M, Mitran C, Mitran M . Advances in Understanding the Immunological Pathways in Psoriasis. Int J Mol Sci. 2019; 20(3). PMC: 6387410. DOI: 10.3390/ijms20030739. View

Chiricozzi A, Romanelli P, Volpe E, Borsellino G, Romanelli M . Scanning the Immunopathogenesis of Psoriasis. Int J Mol Sci. 2018; 19(1). PMC: 5796128. DOI: 10.3390/ijms19010179. View

Buja A, Miatton A, Cozzolino C, Brazzale A, Lo Bue R, Mercuri S . The Prevalent Comorbidome at the Onset of Psoriasis Diagnosis. Dermatol Ther (Heidelb). 2023; 13(9):2093-2105. PMC: 10442308. DOI: 10.1007/s13555-023-00986-0. View

Masson W, Lobo M, Molinero G . Psoriasis and Cardiovascular Risk: A Comprehensive Review. Adv Ther. 2020; 37(5):2017-2033. PMC: 7467489. DOI: 10.1007/s12325-020-01346-6. View

Korman N . Management of psoriasis as a systemic disease: what is the evidence?. Br J Dermatol. 2019; 182(4):840-848. PMC: 7187293. DOI: 10.1111/bjd.18245. View

Hjuler K, Gormsen L, Vendelbo M, Egeberg A, Nielsen J, Iversen L . Increased global arterial and subcutaneous adipose tissue inflammation in patients with moderate-to-severe psoriasis. Br J Dermatol. 2016; 176(3):732-740. DOI: 10.1111/bjd.15149. View

Youn S, Kang S, Kim S, Park G, Lee W . Subclinical systemic and vascular inflammation detected by (18) F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with mild psoriasis. J Dermatol. 2015; 42(6):559-66. DOI: 10.1111/1346-8138.12859. View

10.

Damiani G, Radaeli A, Olivini A, Calvara-Pinton P, Malerba M . Increased airway inflammation in patients with psoriasis. Br J Dermatol. 2016; 175(4):797-9. DOI: 10.1111/bjd.14546. View

11.

Danieli M, Antonelli E, Piga M, Claudi I, Palmeri D, Tonacci A . Alarmins in autoimmune diseases. Autoimmun Rev. 2022; 21(9):103142. DOI: 10.1016/j.autrev.2022.103142. View

12.

Gao Y, Gong B, Chen Z, Song J, Xu N, Weng Z . Damage-Associated Molecular Patterns, a Class of Potential Psoriasis Drug Targets. Int J Mol Sci. 2024; 25(2). PMC: 10815563. DOI: 10.3390/ijms25020771. View

13.

Nakamura K, Sakai S, Tsuyama J, Nakamura A, Otani K, Kurabayashi K . Extracellular DJ-1 induces sterile inflammation in the ischemic brain. PLoS Biol. 2021; 19(5):e3000939. PMC: 8136727. DOI: 10.1371/journal.pbio.3000939. View

14.

Kurpet K, Chwatko G . S100 Proteins as Novel Therapeutic Targets in Psoriasis and Other Autoimmune Diseases. Molecules. 2022; 27(19). PMC: 9572071. DOI: 10.3390/molecules27196640. View

15.

Leclerc E, Heizmann C . The importance of Ca2+/Zn2+ signaling S100 proteins and RAGE in translational medicine. Front Biosci (Schol Ed). 2011; 3(4):1232-62. DOI: 10.2741/223. View

16.

Leclerc E, Fritz G, Vetter S, Heizmann C . Binding of S100 proteins to RAGE: an update. Biochim Biophys Acta. 2009; 1793(6):993-1007. DOI: 10.1016/j.bbamcr.2008.11.016. View

17.

Awad S, Attallah D, Salama R, Mahran A, Abu El-Hamed E . Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis. Clin Exp Dermatol. 2018; 43(3):262-267. DOI: 10.1111/ced.13370. View

18.

Ionita M, Vink A, Dijke I, Laman J, Peeters W, van der Kraak P . High levels of myeloid-related protein 14 in human atherosclerotic plaques correlate with the characteristics of rupture-prone lesions. Arterioscler Thromb Vasc Biol. 2009; 29(8):1220-7. DOI: 10.1161/ATVBAHA.109.190314. View

19.

Shiotsu Y, Mori Y, Nishimura M, Sakoda C, Tokoro T, Hatta T . Plasma S100A12 level is associated with cardiovascular disease in hemodialysis patients. Clin J Am Soc Nephrol. 2011; 6(4):718-23. PMC: 3069361. DOI: 10.2215/CJN.08310910. View

20.

Miettinen T, Pyorala K, Olsson A, Musliner T, Cook T, Faergeman O . Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S). Circulation. 1998; 96(12):4211-8. DOI: 10.1161/01.cir.96.12.4211. View