• I. I. Khudan-Tsilo
  • O. O. Shevchuk
  • M. M. Korda Ternopil State Medical University, Ternopil
Keywords: contact nickel dermatitis, cytokines, nanoparticles, betamethasone, SOD, 1400W.


Background. Inflammation, oxidative and nitro-oxidative stress are the essentials of the pathogenesis of contact allergic dermatitis as well as cytokines imbalance.

Objective. The concentration of TNF-α, IL-1β, IL-4 and IL-10 in blood serum of rats with nickel-induced contact allergic dermatitis was evaluated to determine whether it correlated with the use of free and nanoencapsulated preparations of betamethasone, superoxide dismutase (SOD) and potent highly selective inhibitor of iNOS (1400W).

Methods. To induce contact dermatitis (CD), 5 % nickel sulfate was used for 12 days. Experiments were performed on white inbred male rats, 180–220 g of body mass. All rats were divided into 10 groups (n=10). Group I – the control one; II – the animals with CD; III – the rats with CD treated with empty polymeric chitosan nanoparticles; groups IV–VI – the rats with CD treated with free SOD, 1400W and betamethasone; groups VII-IX – the rats administered with nanoencapsulated SOD, 1400W and betamethasone; X – CD + nano-composition of all agents.

Results. The statistically higher serum concentrations of TNF-α, IL-1β and decrease of IL-4 and IL-10 in experimental contact dermatitis is proved in comparison with the healthy rats. Mono-treatment with betamethasone, SOD and 1400W is efficient, but the use of nanoparticles loaded with these preparations surpasses its effects. The use of the combination of all nanoencapsulated medicines is the most effective.

Conclusions. Chitosan nanoparticles loaded with topical anti-inflammatory glucocorticoid, and inhibitors of oxidative and nitro-oxidative stress is a promising method for treatment of allergic contact dermatitis and can be recommended for further research and use in clinics.


Peiser M, Tralau T, Heidler J, Api AM, Arts JHE, Basketter DA, et al. Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Cell Mol Life Sci 2012;69:763–81. doi:10.1007/s00018-011-0846-8.

Brasch J, Becker D, Aberer W, Bircher A, Kränke B, Jung K, et al. Guideline contact dermatitis. [German]. Allergo J 2014;23:30–43. doi:

Martin SF, Esser PR, Weber FC, Jakob T, Freudenberg MA, Schmidt M, et al. Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergy Eur J Allergy Clin Immunol 2011;66:1152–63. doi:10.1111/j.1398-9995.


Lim HW, Collins SAB, Resneck JS, Bolognia JL, Hodge JA, Rohrer TA, et al. The burden of skin disease in the United States. J Am Acad Dermatol 2017;76:958–972.e2. doi:10.1016/j.jaad.2016.12.043.

Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Gastrointestinal and endocrinologic side effects. J Am Acad Dermatol 2017;76:11–6. doi:10.1016/j.jaad.2016.02.1241.

Dhar S, Seth J, Parikh D. Systemic side-effects of topical corticosteroids. Indian J Dermatol 2014;59:460–4. doi:10.4103/0019-5154.139874.

Rahimi N. Defenders and Challengers of Endothelial Barrier Function. Front Immunol 2017;8:1847. doi:10.3389/fimmu.2017.01847.

Abdel-Mottaleb MM, Try C, Pellequer Y, Lamprecht A, Abdel- MMA, Abdel-Mottaleb MM, et al. Nanomedicine strategies for targeting skin inflammation. Nanomedicine 2014;9:1727–43. doi:10.2217/nnm.14.74.

Bhatia S. Natural polymer drug delivery systems: Nanoparticles, plants, and algae. 2016. doi:10.1007/978-3-319-41129-3.

Siddique MI, Katas H, Amin MCIM, Ng S-F, Zulfakar MH, Buang F, et al. Minimization of Local and Systemic Adverse Effects of Topical Gluco­corticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles. J Pharm Sci 2015;104:4276–86. doi:10.1002/jps.24666.

Fontana MC, Rezer JFP, Coradini K, Leal DBR, Beck RCR. Improved efficacy in the treatment of contact dermatitis in rats by a dermatological nanomedicine containing clobetasol propionate. Eur J Pharm Biopharm 2011;79:241–9. doi:10.1016/j.ejpb.2011.05.002.

Coondoo A, Phiske M, Verma S, Lahiri K. Side-effects of topical steroids: A long overdue revisit. Indian Dermatol Online J 2014;5:416–25. doi:10.4103/2229-5178.142483.

Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol 2016;138:984–1010. doi:10.1016/j.jaci.2016.06.033.

Xiao Z, Xiao S, Zhang Y, Pan T, Ouyang B. The Anti-Inflammatory Effect of Fructus Kochiae on Allergic Contact Dermatitis Rats via pERK1/2/TLR4/NF- kB Pathway Activation. Evidence-Based Complement Altern Med 2018;2018:1–12. doi:10.1155/2018/1096920.

Hussain Z, Katas H, Mohd Amin MCI, Kumolosasi E, Buang F, Sahudin S. Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: An ex vivo and in vivo study using an NC/Nga mouse model. Int J Pharm 2013;444:109–19. doi:10.1016/j.ijpharm.2013.01.024.

Bechara R, Antonios D, Azouri H, Pallardy M. Nickel Sulfate Promotes IL-17A Producing CD4+ T Cells by an IL-23-Dependent Mechanism Regulated by TLR4 and Jak-STAT Pathways. J Invest Dermatol 2017;137:2140–8. doi:10.1016/j.jid.2017.05.025.

Kolesnik M, Franke I, Lux A, Quist SR, Gollnick HP. Eczema in Psoriatico: An Important Differential Diagnosis Between Chronic Allergic Contact Dermatitis and Psoriasis in Palmoplantar Localization. Acta Derm Venereol 2018;98:50–8. doi:10.2340/00015555-2779.

Lagrelius M, Wahlgren C-F, Matura M, Bergström A, Kull I, Lidén C. A population-based study of self-reported skin exposures and symptoms in relation to contact allergy in adolescents. Contact Dermatitis 2017;77:242–9. doi:10.1111/cod.12816.

Yamaguchi H, Kabashima-Kubo R, Bito T, Sakabe J ichi, Shimauchi T, Ito T, et al. High frequencies of positive nickel/cobalt patch tests and high sweat nickel concentration in patients with intrinsic atopic dermatitis. J Dermatol Sci 2013;72:240–5. doi:10.1016/j.jdermsci.2013.07.009.

Khan M, Rani Z, Ahmed M, Hussain I. Evaluation and pattern of nickel dermatitis in patients with allergic contact dermatitis. J Pakistan 2016;15:136–9.

Bordignon V, Palamara F, Altomonte G, Sperduti I, Pietravalle M, Cavallotti C, et al. A laboratory test based on determination of cytokine profiles: a promising assay to identify exposition to contact allergens and predict the clinical outcome in occupational allergic contact dermatitis. BMC Immunol 2015;16:4. doi:10.1186/s12865-015-0066-3.

Elsabahy M, Wooley KL. Cytokines as biomarkers of nanoparticle immunotoxicity. Chem Soc Rev 2013;42:5552–76. doi:10.1039/c3cs60064e.

Cruz CM, Rinna A, Forman HJ, Ventura ALM, Persechini PM, Ojcius DM. ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages. J Biol Chem 2007;282:2871–9. doi:10.1074/jbc.M608083200.

Corsini E, Galli CL. Epidermal cytokines in experimental contact dermatitis. Toxicology 2000;142:203–11. doi:10.1016/S0300-483X(99)00145-6.

Saint-Mezard P, Krasteva M, Chavagnac C, Bosset S, Akiba H, Kehren J, et al. Afferent and Efferent Phases of Allergic Contact Dermatitis (ACD) Can Be Induced After a Single Skin Contact with Haptens: Evidence Using a Mouse Model of Primary ACD. J Invest Dermatol 2003;120:641–7. doi:10.1046/j.1523-1747.2003.12093.x.

Pucheu-Haston CM, Bizikova P, Marsella R, Santoro D, Nuttall T, Eisenschenk MNC. Review: Lymphocytes, cytokines, chemokines and the T-helper 1-T-helper 2 balance in canine atopic dermatitis. Vet Dermatol 2015;26:124-e32. doi:10.1111/vde.12205.

Baranova NI, Kozhenkova SV, Ashchina LA. Role of regulatory T cells in pathogenesis of allergic diseases. Cytokines and Inflammation. 2015;14:12–6 [In Russian].

Alshevskaya AA, Lopatnikova YuA, Shka­ruba NS, Chumasova OA, Sizikov AE, Krugleeva OL, Nepomnyashchikh VM, Vasilyev FF, Sennikov SV. The expression of membrane-bound TNFα receptors on monocytes in atopic dermatitis and rheumatoid arthritis. Cytokines and Inflammation. 2015;14:18–23. [In Russian]

Smolnikova MV, Smirnova SV, Barilo AA, Epaneshnikova VB. Cytokine gene polymorphisms of C-590T IL4 and C-597A IL10 and serum concentrations of IL-4 and IL-10 in psoriasis and psoriatic arthritis. Cytokines and Inflammation. 2016;15:74–80 [In Russian].

Jensen LE. Targeting the IL-1 family members in skin inflammation. Curr Opin Investig Drugs 2010;11:1211–20.

Khudan-Tsilo II, Shevchuk OO, Korda MM. Topical treatment of contact nickel dermatitis: capasity of nanoencapsulated superoxide dismutase. Bulletin of Scientific Data 2017;4:140–4 [In Ukrainian].

Khudan-Tsilo II, Korda MM. Structural changes in contact nickel dermatitis in case of suppressing of iNOS. Achievements of Clinical and Experimental Medicine. 2017;3:165–9. doi:10.11603/1811-2471.2017.v1.i3.8177 [In Ukrainian].

Wilsmann-Theis D, Koch S, Mindnich C, Bonness S, Schnautz S, von Bubnoff D, et al. Generation and functional analysis of human TNF-α/iNOS-producing dendritic cells (Tip-DC). Allergy 2013;68:890–8. doi:10.1111/all.12172.

Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines Of Care For The Management Of Atopic Dermatitis: Part 2: Management and Treatment of Atopic Dermatitis with Topical Therapies. J Am Acad Dermatol 2014;71:116–32. doi:10.1016/j.jaad.2014.03.023.

Lo Faro ML, Fox B, Whatmore JL, Winyard PG, Whiteman M. Hydrogen sulfide and nitric oxide interactions in inflammation. Nitric Oxide 2014;41:38–47. doi:10.1016/j.niox.2014.05.014.

Khudan-Tsilo II, Korda MM. Nano-form of superoxide dismutase - perspective method of treatment of contact dermatitis. Bulletin of Scientific Data 2017;3:144–8. doi:10.11603/2415-8798.2017.3.8135 [In Ukrainian].

How to Cite
Khudan-Tsilo, I., Shevchuk, O., & Korda, M. (2018). CYTOKINES PROFILE IN EXPERIMENTAL CONTACT ALLERGIC DERMATITIS AND USE OF NANOENCAPSULATED PREPARATIONS. International Journal of Medicine and Medical Research, (1).
Biomedical Sciences