The effect of cigarette smoking on serum levels of regulatory cytokines and molecules involved in atherogenesis during systemic treatment of psoriasis – results of a preliminary study
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Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Poland
Department of Ecology and Environmental Protection, Faculty of Biology and Biotechnology, University of Warmia nad Mazury in Olsztyn, Poland
Department of Dermatology, Military Institute of the Health Services in Warsaw, Poland
Department of Gynecology and Obstetrics, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Poland
Submission date: 2020-12-27
Final revision date: 2021-03-09
Acceptance date: 2021-03-10
Online publication date: 2021-08-20
Corresponding author
Natalia Zdanowska   

Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, School of Medicine, Collegium Medicum, The University of Warmia and Mazury in Olsztyn, Wojska Polskiego 30, 10-229 Olsztyn, Poland. Tel.: +48502232591.
Pol. Ann. Med. 2021;28(2):141-149
Among the diseases associated with psoriasis linked to smoking are primarily cardiovascular diseases (including atherosclerosis) and metabolic syndrome. In addition, cigarette smoking also affects the effectiveness of systemic treatment of psoriasis.

Assessment of the effect of cigarette smoking on biomarkers of atherosclerosis in patients with psoriasis treated with methotrexate and adalimumab.

Material and methods:
The serum levels of vascular cell adhesion molecule 1 (VCAM-1), E-selectin, oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibodies, IL-10, IL-35, TGFß1, were assessed in 34 patients with psoriasis (15 smokers and 19 non-smokers), and 8 healthy, non-smoking volunteers.

Results and discussion:
Smoking patients had significantly higher body mass index, lower high density lipoprotein (HDL), higher risk of 10-year fatal cardiovascular disease, higher IL-10 levels and lower IL-35 levels at baseline compared to healthy, non-smoking volunteers. We observed decreases in IL-10, VCAM-1, E-selectin, and oxLDL levels during 12 weeks of methotrexate treatment and, a decrease in IL-35 during adalimumab treatment, based on enzyme-linked immunosorbent assays.

Our results indicate the need for a holistic approach to psoriasis treatment that includes lifestyle modifications like smoking cessation to slow the development of atherosclerosis and increase the possibility of improving skin lesions.

This study was supported by the Ministry of Science and Higher Education, Poland (grant No. 61.610. 001-300).
Zbigniew Swacha cooperates with Medac. Other authors declare no conflict of interests. Both funders and Medac had no influence on the research project, collection, analysis and interpretation of the results obtained, manuscript writing and the decision to publish the obtained conclusions.
Lønnberg AS, Skov L, Skytthe A, Kyvik KO, Pedersen OB, Thomsen SF. Smoking and risk for psoriasis: A population-based twin study. Int J Dermatol. 2016;55(2):e72–78.
Warner KE, Mendez D. How much of the future mortality toll of smoking can be avoided? Tob Control. 2021;30:456–459.
Richer V, Roubille C, Fleming P, et al. Psoriasis and smoking: A systematic literature review and meta-analysis with qualitative analysis of effect of smoking on psoriasis severity. J Cutan Med Surg. 2016;20(3):221–227.
Rui W, Xiangyu D, Fang X, et al. Metabolic syndrome affects narrow-band UVB phototherapy response in patients with psoriasis. Medicine (Baltimore). 2017;96(50):e8677. 10.1097/MD.0000000000008677.
Batalla A, González-Fernández D, González-Lara L, et al. Cardiovascular risk factors influence response to biological therapies in psoriasis. J Am Acad Dermatol. 2015;73(2):327–329.
Armstrong AW, Harskamp CT, Dhillon JS, Armstrong EJ. Psoriasis and smoking: A systematic review and meta-analysis. Br J Dermatol. 2014;170(2):304–314.
Jin Y, Yang S, Zhang F, et al. Combined effects of HLA-Cw6 and cigarette smoking in psoriasis vulgaris: A hospital-based case-control study in China. J Eur Acad Dermatol Venereol. 2009;23(2):132–137.
Højgaard P, Glintborg B, Hetland ML, et al. Association between tobacco smoking and response to tumour necrosis factor α inhibitor treatment in psoriatic arthritis: Results from the DANBIO registry. Ann Rheum Dis. 2015;74(12):2130–2136.
Naldi L. Psoriasis and smoking: Links and risks. Psoriasis (Auckl). 2016;6:65–71.
Bălănescu AR, Bojincă VC, Bojincă M, Donisan T, Bălănescu SM. Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases. Exp Ther Med. 2019;17(2):1024–1029.
Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS. Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol. 2005;52(2):262–267.
Chin YY, Yu HS, Li WC, et al. Arthritis as an important determinant for psoriatic patients to develop severe vascular events in Taiwan: A nation-wide study. J Eur Acad Dermatol Venereol. 2013;27(10):1262–1268.
Oberoi R, Schuett J, Schuett H, et al. Targeting tumor necrosis factor-α with adalimumab: Effects on endothelial activation and monocyte adhesion. PLoS One. 2016;11(7):e0160145.
Wu JJ, Guérin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81–90.
Yang ZS, Lin NN, Li L, Li Y. The effect of TNF inhibitors on cardiovascular events in psoriasis and psoriatic arthritis: An updated meta-analysis. Clin Rev Allergy Immunol. 2016;51(2):240–247.
Curtis JR, Danila MI, Chen L, et al. Risk of cardiovascular outcomes among psoriasis patients treated with biologics and other systemic agents. J Psoriasis Psoriatic Arthritis. 2016;1(3):128–137.
Gazel U, Ayan G, Solmaz D, Akar S, Aydin SZ. The impact of smoking on prevalence of psoriasis and psoriatic arthritis. Rheumatology (Oxford). 2020;59(10):2695–2710.
Pezzolo E, Naldi L. The relationship between smoking, psoriasis and psoriatic arthritis. Expert Rev Clin Immunol. 2019;15(1):41–48.
Nguyen UDT, Zhang Y, Lu N, et al. Smoking paradox in the development of psoriatic arthritis among patients with psoriasis: A population-based study. Ann Rheum Dis. 2018;77(1):119–123.
Varona JF, Ortiz-Regalón R, Sánchez-Vera I, et al. Soluble ICAM 1 and VCAM 1 blood levels alert on subclinical atherosclerosis in non smokers with asymptomatic metabolic syndrome. Arch Med Res. 2019;50(2):20–28. 10.1016/j.arcmed.2019.05.003.
Pletsch-Borba L, Grafetstätter M, Hüsing A, et al. Biomarkers of vascular injury in relation to myocardial infarction risk: A population-based study. Sci Rep. 2019;9:3004.
Genre F, Armesto S, Corrales A, et al. Significant sE-Selectin levels reduction after 6 months of anti-TNF-α therapy in non-diabetic patients with moderate-to-severe psoriasis. J Dermatol Treat. 2017;28:726–730.
Lin J, Kakkar V, Lu X. The role of interleukin 35 in atherosclerosis. Curr Pharm Des. 2015;21(35):5151–5159.
Pan X, Xu K, Li Y, et al. Interleukin-35 expression protects against cigarette smoke-induced lung inflammation in mice. Biomed Pharmacother. 2019;110:727–732.
Ugur MG, Kutlu R, Kilinc I. The effects of smoking on vascular endothelial growth factor and inflammation markers: A case-control study. Clin Respir J. 2018;12(5):1912–1918.
Khimion LV, Boiko AV. Features of the interconnection of traditional risk factors and il-10 with the activity of the inflammatory process and atherosclerosis development in patients with psoriatic arthritis. Wiad Lek. 2020;73(5):914–919.
Sepehri ZS, Masoomi M, Ruzbehi F, et al. Comparison of serum levels of IL-6, IL-8, TGF-β and TNF-α in coronary artery diseases, stable angina and participants with normal coronary artery. Cell Mol Biol (Noisy-le-grand). 2018;64(5):1–6.
Talbot M, Hamel-Auger M, Beaulieu MJ, et al. Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice. Respir Res. 2018;19:131.
Kassi E, Dalamaga M, Faviou E, et al. Circulating oxidized LDL levels, current smoking and obesity in postmenopausal women. Atherosclerosis. 2009;205(1):279–283.
Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: An update. J Am Coll Cardiol. 2004;43:1731–1737.
Andican G, Seven A, Uncu M, Cantaşdemir M, Numan F, Burçak G. Oxidized LDL and anti-oxLDL antibody levels in peripheral atherosclerotic disease. Scand J Clin Lab Invest. 2008;68(6):473–478.
Thayaparan D, Shen P, Stämpfli MR, Morissette MC. Induction of pulmonary antibodies against oxidized lipids in mice exposed to cigarette smoke. Respir Res. 2016;17:97.
Kim K, Lim C, Kim G, et al. Association of plasma marker of oxidized lipid with histologic plaque instability in patients with peripheral artery disease. Ann Vasc Surg. 2020;66:554–565.
Tekin NS, Tekin IO, Barut F, Sipahi EY. Accumulation of oxidized low-density lipoprotein in psoriatic skin and changes of plasma lipid levels in psoriatic patients. Mediators Inflamm. 2007;2007:78454.
Gisondi P, Cotena C, Tessari G, Girolomoni G. Anti-tumour necrosis factor-α therapy increases body weight in patients with chronic plaque psoriasis: A retrospective cohort study. J Eur Acad Dermatol Venereol. 2008;22(3):341–344. 10.1111/j.1468-3083.2007.02429.x.
Zdanowska N, Owczarczyk-Saczonek A, Czerwińska J, et al. Adalimumab and methotrexate affect the concentrations of regulatory cytokines (interleukin-10, transforming growth factor-β1, and interleukin-35) in patients with plaque psoriasis. Dermatol Ther. 2020;33(6):e14153.
Zdanowska N, Owczarczyk-Saczonek A, Czerwińska J, et al. Methotrexate and adalimumab decrease the serum levels of cardiovascular disease biomarkers (VCAM-1 and E-Selectin) in plaque psoriasis. Medicina (Kaunas). 2020;56(9):E473.
Hercogová J, Ricceri F, Tripo L, Lotti T, Prignano F. Psoriasis and body mass index. Dermatol Ther. 2010;23(2):152–154.
Hu SC, Lan CE. Psoriasis and cardiovascular comorbidities: Focusing on severe vascular events, cardiovascular risk factors and implications for treatment. Int J Mol Sci. 2017;18(10):2211.
Semenov YR, Herbosa CM, Rogers AT, et al. Psoriasis and mortality in the US: Data from the National Health and Nutrition Examination Survey. J Am Acad Dermatol. 2019;S0190-9622(19)32558-7.
Adışen E, Uzun S, Erduran F, Gürer MA. Prevalence of smoking, alcohol consumption and metabolic syndrome in patients with psoriasis. An Bras Dermatol. 2018;93(2):205–211.
Szurkowska M. Influence of lifestyle on the levels of insulin in healthy people. In: Szybiński Z, ed. The Insulin Levels in the Metabolic Syndrome. Kraków: Wyd. Medyczne; 2003:109–126.
Wierzejewska R, Jarosz M. [Is smoking effective in weight control – review of the literature]. Przegl Lek. 2008;65: 692–694 [in Polish].
Wu M-Y, Yu C-L, Yang S-J, Chi C-C. Change in body weight and body mass index in psoriasis patients receiving biologics: A systematic review and network meta-analysis. J Am Acad Dermatol. 2020;82(1):101–109.
Anzengruber F, Augustin M, Radtke MA, et al. Smoking does not alter the therapy response to systemic anti-psoriatic therapies: A two-country, multi-centre, prospective, non-interventional study. Acta Derm Venereol. 2019;99(10):871–877.
Owczarczyk-Saczonek A, Nowicki R. The association between smoking and the prevalence of metabolic syndrome and its components in patients with psoriasis aged 30 to 49 years. Adv Dermatol Allergol/Postępy Dermatol Alergol. 2015;32(5):331–336.
Teixeira GG, Mari NL, de Paula JCC, et al. Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis. Clin Exp Med. 2020;20:39–48.
Szepietowski JC, Wąsik F, Bielicka E, Nockowski P, Noworolska A. Soluble E‐selectin serum levels correlate with disease activity in psoriatic patients. Clin Exp Dermatol. 1999;24:33–36. 00401.x.
Czech W, Schöpe E, Kapp A. Soluble E-selectin in sera of patients with atopic dermatitis and psoriasis--correlation with disease activity. Br J Dermatol. 1996;134(1):17–21.
Gkalpakiotis S, Arenbergerova M, Gkalpakioti P, Potockova J, Arenberger P, Kraml P. Impact of adalimumab treatment on cardiovascular risk biomarkers in psoriasis: Results of a pilot study. J Dermatol. 2017;44(4):363–369.
Michalak S, Rybacka J, Wysocka E, Kozubski W. Palenie tytoniu a poziom krazacej E-selektyny u chorych z migrena [The effect of tobacco smoking on the levels of circulating E-selectin in migraineurs]. Przegl Lek. 2010;67(10):897–900 [in Polish].
Hambardzumyan K, Bolce RJ, Wallman JK, van Vollenhoven RF, Saevarsdottir S. Serum biomarkers for prediction of response to methotrexate monotherapy in early rheumatoid arthritis: Results from the SWEFOT Trial. J Rheumatol. 2019;46(6):555–563.
Coimbra S, Oliveira H, Reis F, et al. Circulating levels of adiponectin, oxidized LDL and C-reactive protein in Portuguese patients with psoriasis vulgaris, according to body mass index, severity and duration of the disease. J Dermatol Sci. 2009;55(3):202–204.
Ogawa K, Tanaka T, Nagoshi T, et al. Increase in the oxidised low-density lipoprotein level by smoking and the possible inhibitory effect of statin therapy in patients with cardiovascular disease: A retrospective study. BMJ Open. 2015;5:e005455.
Örem A, Çimşit G, Değer O, Örem C, Vanizor B. The significance of autoantibodies against oxidatively modified low-density lipoprotein (LDL) in patients with psoriasis. Clin Chim Acta. 1999;284:81–88.
Aspera-Werz RH, Chen T, Ehnert S, Zhu S, Fröhlich T, Nussler AK. Cigarette smoke induces the risk of metabolic bone diseases: Transforming growth factor beta signaling impairment via dysfunctional primary cilia affects migration, proliferation, and differentiation of human mesenchymal stem cells. Int J Mol Sci. 2019;20(12):2915.
Owczarczyk-Saczonek A, Czerwińska J, Placek W. The role of regulatory T cells and anti-inflammatory cytokines in psoriasis. Acta Dermatovenerol Alp Pannonica Adriat. 2018;27(1):17–23.
Georgescu S-R, Tampa M, Caruntu C, et al. Advances in understanding the immunological pathways in psoriasis. Int J Mol Sci. 2019;20(3):739.
Owczarczyk-Saczonek A, Czerwińska J, Orylska M, Placek W. Evaluation of selected mechanisms of immune tolerance in psoriasis. Postepy Dermatol Alergol. 2019;36(3):319–328.
Jiang S, Shan F, Zhang Y, Jiang L, Cheng Z. Increased serum IL-17 and decreased serum IL-10 and IL-35 levels correlate with the progression of COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:2483–2494.
Li T, Gu M, Liu P, et al. Clinical significance of weak interleukin-35 expression in patients with psoriasis. Microbiol Immunol. 2018;62(7):454–461.
Olsson P, Skogstrand K, Nilsson A, et al. Smoking, disease characteristics and serum cytokine levels in patients with primary Sjögren’s syndrome. Rheumatol Int. 2018;38(8):1503–1510.
Solberg SM, Sandvik LF, Eidsheim M, Jonsson R, Bryceson YT, Appel S. Serum cytokine measurements and biological therapy of psoriasis – Prospects for personalized treatment? Scand J Immunol. 2018;88(6):e12725.
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