Dynamics of blood cytokine profile in patients with psoriatic arthritis and metabolic syndrome during different types of treatment

Objective - to study the dynamics of blood cytokine profile parameters in patients with psoriatic arthritis and metabolic syndrome during complex treatment with tofacinib and various types of physiotherapy. Materials and methods. The study involved 230 patients with psoriatic arthritis with signs of metabolic syndrome (mean age 55.3±7.0 years; 111 men and 119 women). The patients were divided into five groups: the first group received standard drug therapy (Ct), the second group received Ct and tofacitinib (Top+Ct), the third is Ct and plantar laser blood irradiation (NLOC+Ct), the fourth is Ct and phototherapy (Ft+Ct), the fifth is combined treatment (Top+NLK+Ft+Ct). The content of IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17, IL-18, IL-23, TNF-α and INF-γ in the blood serum of patients was determined by enzyme immunoassay before treatment, as well as 3 and 6 months after its start. Results. It was found that standard treatment did not cause significant changes in all the studied parameters at all follow-up periods. In the remaining groups, 3 months after the start of treatment, there was a significant decrease in blood levels of IL-1b, IL-2, IL-6, IL-8, IL-13, IL-17, IL-18, IL-23, TNF-α, INF-γ against the background of increased levels of IL-4 and IL-10 were most pronounced in the group of Top+NLC+Ft+Ct. In this group, cytokine levels significantly differed from those of other types of treatment at all follow-up periods. This fact may indicate a summation of the effects of different types of therapeutic effects when exposed to different pathogenetic links of the disease. At the same time, no significant differences were found in all groups of patients when comparing their indicators 3 and 6 months after the start of treatment, which indicates that there were no significant changes in their dynamics during this period. Conclusion. The use of standard treatment alone in patients with psoriatic arthritis with metabolic syndrome did not change the blood levels of the studied pro-inflammatory and anti-inflammatory cytokines 3 and 6 months after the start of treatment. The use of additional medicinal (tofacitinib) and non-medicinal (laser therapy, phototherapy) effects against the background of standard therapy caused significant changes in the studied parameters at all follow-up periods, with the most pronounced effect in a subgroup of patients with complex use along with standard treatment of tofacitinib, laser therapy and phototherapy.

1. Petrova M.S., Sukhova T.E. Patients with psoriasis at a dermatologist's appointment. Opinion Leader. 2021;(1):56-67 (in Russ.). EDN: JDVZRJ.

2. Alinaghi F., Calov M., Kristensen L.E., Gladman D.D., Coates L.C., Jullien D., Gottlieb A.B., Gisondi P. et al. Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol. 2019;80(1):251-265.e19. DOI: 10.1016/j.jaad.2018.06.027.

3. Azuaga A.B., Ramírez J., Cañete J.D. Psoriatic Arthritis: Pathogenesis and Targeted Therapies.Int J Mol Sci. 2023;24(5):4901. DOI: 10.3390/ijms24054901.

4. Gisondi P., Tessari G., Conti A., Piaserico S., Schian-chi S., Peserico A., Giannetti A., Girolomoni G. Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case-control study. Br J Dermatol. 2007;157(1):68-73. DOI: 10.1111/j.1365-2133.2007.07986.x.

5. Herron M.D., Hinckley M., Hoffman M.S., Papenfuss J., Hansen C.B., Callis K.P., Krueger G.G. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol. 2005;141(12):1527-1534. DOI: 10.1001/archderm.141.12.1527.

6. Malesci D., Valentini G., La Montagna G. La sindrome metabolica nelle malattie reumatiche infiammatorie [Metabolic syndrome in inflammatory rheumatic diseases]. Reumatismo. 2006 Jul-Sep;58(3):169-176. DOI: 10.4081/reumatismo.2006.169. (in Ital.).

7. Mallbris L., Granath F., Hamsten A., Ståhle M. Psoriasis is associated with lipid abnormalities at the onset of skin disease. J Am Acad Dermatol. 2006;54(4): 614-621. DOI: 10.1016/j.jaad.2005.11.1079.

8. Gottlieb A.B., Chao C., Dann F. Psoriasis comorbidities. J Dermatolog Treat. 2008;19(1):5-21. DOI: 10.1080/09546630701364768.

9. Hagège B., Tan E., Gayraud M., Fautrel B., Gossec L., Mitrovic S. Remission and low disease activity in psoriatic arthritis publications: a systematic literature review with meta-analysis. Rheumatology (Oxford). 2020;59(8):1818-1825. DOI: 10.1093/rheumatology/keaa030.

10. Novikov P.I., Moiseev S.V. Janus-kinase inhibitors in rheumatoid and psoriatic arthritis and other rheumatic diseases. Klinicheskaya farmakologiya i terapiya. 2020;29(1): 41-47 (in Russ.). DOI: 10.32756/0869-5490-2020-1-41-47. EDN: IHKKDC.

11. Nasonov E., Avdeeva A.S., Lila A.M. Efficacy and safety of tofacitinib for immune-mediated inflammatory rheumatic diseases (Part I). Nauchno-prakticheskaya revmatologiya. 2020;58(1): 62-79 (in Russ.). DOI: 10.14412/1995-4484-2020-62-79. EDN: ZKSSVD.

12. Ali L.Kh.M. Psoriatic arthritis (etiopathogenesis, diagnosis, treatment). Dermatovenerologiya. Kosmetologiya. Seksopatologiya. 2011;(1):95-101 (in Russ.)

13. Yazkova O.S., Anpilogova E.M. Phototherapy for psoriasis.Russian Journal of Skin and Venereal Diseases. 2022;25(1):29-39 (in Russ.). DOI: 10.17816/dv105476. EDN: TCUTUD.

14. Nikolashina O.E. Effect of combined application of narrowband UVB phototherapy and lefl unomide on factors. Fizioterapevt. 2017;(4):69-75 (in Russ.). EDN: ZUCYPN

15. Bogolyubov V.M., Sidorov V.D. Physiotherapy in the rehabilitation of patients with rheumatoid arthritis. Fizioterapiya, bal'neologiya i reabilitatsiya. 2012;(1):3-9 (in Russ.). EDN: PGPGOD.

16. Yevstratova Ye.F., Nikitin A.V., Vasil'yeva L.V., Orlova Ye.V. Influence of combined therapy with low intensity laser radiation and anti-tumor necrosis factor-α (artrofoon) on clinical and laboratory estimates of patients with joint disorders. Sistemnyy analiz i upravleniye v biomeditsinskikh sistemakh. 2008;7(2):440-444 (in Russ.). EDN: JUQWZH.

17. Mease P.J., Antoni C.E. Psoriatic arthritis treatment: biological response modifiers. Ann Rheum Dis. 2005;64 Suppl 2(Suppl 2):ii78-82. DOI: 10.1136/ard.2004.034157.

18. Keller C., Webb A., Davis J. Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review. Ann Rheum Dis. 2003;62(12):1128-1132. DOI: 10.1136/ard.2003.011023.

19. Ketlinskiy S.A., Simbirtsev A.S. Cytokines. Sankt-Peterburg: Foliant, 2008. 552 s. (in Russ.)

20. Korotayeva T.V., Loginova Ye.Yu., Novikov A.A., Klimova N.V., Aleksandrova Ye.N., Erdes Sh.F., Denisov L.N., Nasonov Ye.L. et al. Cytokine profile in psoriatic arthritis: search for relationships with inflammation and blood rheological properties. Nauchno-prakticheskaya revmatologiya. 2011;(1):27-32 (in Russ.). EDN: NTFVLP.

21. Li J., Li D., Tan Z. The expression of interleukin-17, interferon-gamma, and macrophage inflammatory protein-3 alpha mRNA in patients with psoriasis vulgaris. J Huazhong Univ Sci Technolog Med Sci. 2004;24(3):294-296. DOI: 10.1007/BF02832018.

22. Asadullah K., Sabat R., Friedrich M., Volk H.D., Sterry W.Interleukin-10: an important immunoregulatory cytokine with major impact on psoriasis. Curr Drug Targets Inflamm Allergy. 2004;3(2):185-192. DOI: 10.2174/1568010043343886.

23. Alenius G.M., Eriksson C., Rantapää Dahlqvist S.Interleukin-6 and soluble interleukin-2 receptor alpha-markers of inflammation in patients with psoriatic arthritis? Clin Exp Rheumatol. 2009;27(1):120-123.

24. Fraser A., Fearon U., Billinghurst R.C., Ionescu M., Reece R., Barwick T., Emery P., Poole A.R. et al. Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: relationship to mediators of systemic and local inflammation. Arthritis Rheum. 2003;48(11):3085-3095. DOI: 10.1002/art.11331.

25. Balding J., Kane D., Livingstone W., Mynett-Johnson L., Bresnihan B., Smith O., FitzGerald O. Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum. 2003;48(5):1408-1413. DOI: 10.1002/art.10935.

26. Piskin G., Tursen U., Sylva-Steenland R.M., Bos J.D., Teunissen M.B. Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a decrease in the expression of IFN-gamma inducers -- IL-12, IL-18 and IL-23. Exp Dermatol. 2004;13(12):764-772. DOI: 10.1111/j.0906-6705.2004.00246.x.

27. Danning C.L., Illei G.G., Hitchon C., Greer M.R., Boumpas D.T., McInnes I.B. Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis. Arthritis Rheum. 2000;43(6):1244-1256. DOI: 10.1002/1529-0131(200006)43:6<1244::AID-ANR7>3.0.CO;2-2.

28. Drouart M., Saas P., Billot M., Cedoz J.P., Tiberghien P., Wendling D., Toussirot E. High serum vascular endothelial growth factor correlates with disease activity of spondylarthropathies. Clin Exp Immunol. 2003;132(1):158-162. DOI: 10.1046/j.1365-2249.2003.02101.x.

29. Zadionchenko V.S., Adasheva T.V., Sandomirskaya A.P. Endothelial dysfunction and arterial hypertension: therapeutic possibilities. RMJ. 2002;(1):11 (in Russ.). URL: https://www.rmj.ru/articles/kardiologiya/Disfunkciya_endoteliya_i_arterialynaya_gipertoniya_terapevticheskie_vozmoghnosti/

30. Sidigin Ya.A., Lukina G.V. Biological therapy in rheumatology. Moscow: Prakt. meditsina, 2009. 303 p. (in Russ.)

31. Yasumoto S., Imayama S., Hori Y. Increased serum level of interleukin-6 in patients with psoriatic arthritis and thrombocytosis. J Dermatol. 1995;22(10): 718-722. DOI: 10.1111/j.1346-8138.1995.tb03908.x.

32. Kane D., FitzGerald O. Tumor necrosis factor-alpha in psoriasis and psoriatic arthritis: a clinical, genetic, and histopathologic perspective. Curr Rheumatol Rep. 2004;6(4):292-298. DOI: 10.1007/s11926-004-0041-0.

33. Ritchlin C., Haas-Smith S.A., Hicks D., Cappuccio J., Osterland C.K., Looney R.J. Patterns of cytokine production in psoriatic synovium. J Rheumatol. 1998;25(8):1544-1552.

34. Spadaro A., Rinaldi T., Riccieri V., Valesini G., Taccari E.Interleukin 13 in synovial fluid and serum of patients with psoriatic arthritis. Ann Rheum Dis. 2002;61(2):174-176. DOI: 10.1136/ard.61.2.174.

35. Rooney T., Murphy E., Benito M., Roux-Lombard P., FitzGerald O., Dayer J.M., Bresnihan B. Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis. Ann Rheum Dis. 2004;63(11):1393-1398. DOI: 10.1136/ard.2003.016428.

36. Wei C.C., Chen W.Y., Wang Y.C., Chen P.J., Lee J.Y., Wong T.W., Chen W.C., Wu J.C. et al. Detection of IL-20 and its receptors on psoriatic skin. Clin Immunol. 2005;117(1):65-72. DOI: 10.1016/j.clim.2005.06.012.

37. Tobin A.M., Kirby B. TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. BioDrugs. 2005;19(1):47-57. DOI: 10.2165/00063030-200519010-00006.