Abstract
Background
Psoriasis is one of the most common, immune-mediated, chronic inflammatory skin diseases. Proinflammatory cytokines play an important pathogenetic role at a local level.
Objective
To assess whether the proinflammatory cytokines IL-1β, IL-6, IL-17, IL-22 and TNF-α are released systemically during psoriasis.
Methods
Peripheral blood mononuclear cells (PBMCs) were isolated from 30 patients with psoriasis and 30 healthy volunteers. Cytokine production was assessed in supernatants using an enzyme immunoassay after stimulation of PBMCs with microbial stimuli. In addition, flow cytometry was used to determine the subsets of monocytes involved and the intracellular TNF-α production in monocytes.
Results
IL-17 levels were significantly higher in the supernatants of PBMCs from psoriatic patients after stimulation with phytohemagglutinin. TNF-α production was also significantly higher in cells from psoriatic patients after stimulation with all stimuli, as compared with health volunteers. Similar changes were not found for the other cytokines. A statistically significant difference was observed between patients and controls for inflammatory CD14+/CD16+ monocytes (p<0.0001) and patrolling CD14-/CD16+ monocytes.
Conclusion
Hyper-production of TNF-α is documented in psoriasis. These results support the concept that there is a systemic, proinflammatory component in psoriasis.
Similar content being viewed by others
References
Schön MP, Boehncke WH. Psoriasis. N Engl J Med 2005; 352: 189912.
Krueger JG, Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis 2005; 64 (Suppl 2): ii30–6.
Das RP, Jain AK, Ramesh V. Current concepts in the pathogenesis of psoriasis. Indian J Dermatol 2009; 54: 7–12.
Grossman RM, Krueger J, Yourish D, et al. Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Sci USA 1989; 86: 6367–71.
Dowlatshahi EA, van der Voort EA, Arends LR, Nijsten T. Markers of systemic inflammation in psoriasis: a systemic review and metaanalysis. Br J Dermatol 2013; 169: 266–82.
Gomi T, Shiohara T, Munakata T, et al. Interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma in psoriasis. Arch Dermatol 1991; 127: 827–30.
Stoma AM, Bartosinska J, Kowal M, et al. Serum levels of selected Th17 and Th22 cytokines in psoriatic patients. Disease Markrs 2013; 6: 625–31.
Uyemura K, Yamamura M, Fivenson DF, et al. The cytokine networkin lesional and lesion-free psoriatic skin is characterized by a T-helper type 1cell-mediated response. J Invest Dermatol 1993; 101: 701–5.
Steinhoff M, Lugeer TA. The skin cytokine network. In: Bos JD, ed. Skin immune system. Cutaneous Immunology and Clinical Immunodermatology, 3rd ed.. Boca Raton, Florida: CRC Press, 2005, p. 349–72.
Martin DA, Towne JE, Kricorian G, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol 2013; 133: 17–26.
Pan HF, Xiang PL, Zheng SG, Ye DQ. Emerging role ofinterleukin-22 in autoimmune diseases. Cytokine Growth Faccor Rev 2013; 24: 51–7.
Liang SC, Tan XY, Luxenberg DP, et al. Interleukin (IL-22) and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006; 203: 2271–9.
Zheng Y, Danilenko DM, Valdez P, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23 induced dermal inflammation and acanthosis. Nature 2007; 445: 648–51.
Pfeffer K, Matsuyama T, Kundig TM, et al. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 1993; 73: 457–67.
Flynn JL, Goldstein MM, Chan J, et al. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 1995; 6: 561–72.
Girolomoni G, Pastore S, Albanesi C, et al. Targeting tumor necrosis factor-a as a potential therapy in skin inflammatory skin diseases. Curr Opin Investig Drugs 2002; 3: 1590–5.
Sterry W, Barker J, Boehncke WH, et al. Biological therapies in the systemic management of psoriasis: International Consensus Conference. Br J Dermatol 2004; 151(Suppl 69): 3–17.
Boehncke N, Brasie RA, Barker J, et al. Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus. J Eur Acad Dermatol Venereol 2006; 20: 988–98.
Gottlieb AB, Evans R, Li S, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized double-blind, placebo-controlled trial. J Am Acad Dermatol 2004; 51: 543–52.
Gottlieb AB, Hamilton T, Carol I, et al, & Efalizumab Study Group. Long term continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis. J Am Acad Dermatol 2006; 54: 5154–63.
Wollina U, Konrad H. Treatment of recalcitrant psoriatic arthritis with anti-tumor necrosis factor-alpha antibody. J Eur Acad Dermatol Venereol 2002; 16: 127–9.
Cantini F, Niccoli L, Cassarà E, et al. Sustained maintenance of clinical remission after adalimumab dose reduction in patients with early psoriatic arthritis: a long term follow-up study. Biologics 2012; 6: 201–6.
Vollmer S, Menssen A, Trommler P, et al. T lymphocytes derived from skin lesions of patients with psoriasis vulgaris express a novel cytokine pattern that is distinct from that of T helper type 1 and T helper type 2 cells. Eur J Immunol 1994; 24: 2377–82.
Olaniran AK, Baker BS, Paige DG, et al. Cytokine expression in psoriatic skin lesions during PUVA therapy. Arch Dermatol Res 1996; 288: 421–5.
Berstein LE, Berry J, Kim S, et al. Effect of etanercept in patients with metabolic syndrome. Arch Intern Med 2006; 35: 107–11.
Cauza E, Causa K, Hanusch-Enserer U, et al. Intravenous anti -TNF-alpha antibody therapy leads to elevated triglyceride and reduced HDL-cholesterol levels in patients with rheumatoid and psoriatic arthritis. Wien Klin Wochenschr 2002; 114: 1004–7.
Strober B, Berger E, Cather J, et al. A series of critically challenging case scenarios in moderate to severe psoriasis: a Delphi consensus approach. J Am Acad Dermatol 2009; 61: 1–46.
Marks R, Barton S, Shuttleworth D, Finlay AY. Assessment of disease progress in psoriasis. Arch Dermatol 1989; 125: 235–50.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)-a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: 210–6.
Schuerwegh AJ, Stevens WJ, Bridts CH, De Clerk LS. Evaluation of Monensin and Brefeldin A for flow cytometric determination of Interleukin-1 beta, Interleukin-6, and Tumor necrosis factor-alpha in monocytes. Cytometry 2001; 46: 172–6.
Netea MG, Nold-Petry CA, Nold MF, et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages. Blood 2009; 113: 2324–35.
Bonifati C, Ameglio F. Cytokines in psoriasis. Int J Dermatol 1999; 38: 241–51.
De Rie MA, Goedkoop AY, Bos JD. Overviewof psoriasis. Dermatol Ther 2004; 17: 341–9.
Prinz JC. Which T cells cause psoriasis? Clin Exp Dermatol 1999; 24: 291–5.
Witowski J, Ksiazek K, Jorres A. Interleukin-17: a mediator of inflammatory responses. Cell Mol Life Sci 2004; 61: 567–79.
Arican O, Aral M, Sasmaz S, Ciragil P. Serum levels of TNF-a, IFN-γ, IL-6, IL-8, IL-12, IL-17 and IL-18 in patients with active psoriasis and correlation with disease severity. J Med Inflammation 2005; 5: 273–9.
Abdel-Hamid MF, Aly DG, Saad NE, et al. Serum levels of interleukin-8, tumor necrosis factor-α and γ-interferon in Egyptian psoriatic patients and correlation with disease severity. J Dermatol 2011; 38: 442–6.
Helle M, Brakenhoff JPT, DeGroot ER, et al. Interleukin-6 is involved in interleukin-1 induced activities. Eur J Immunol 1988; 18: 957–9.
Boniface K, Guignouard E, Pedretti N, et al. Arole for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol 2007; 150: 407–15.
Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol 1992; 10: 411–52.
Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med 1996; 334: 1717–25.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Kouris, A., Pistiki, A., Katoulis, A. et al. Proinflammatory cytokine responses in patients with psoriasis. Eur Cytokine Netw 25, 63–68 (2014). https://doi.org/10.1684/ecn.2014.0358
Published:
Issue Date:
DOI: https://doi.org/10.1684/ecn.2014.0358