Lymphocyte expression of CD4+CD25hi and adhesion molecules in children with Atopic dermatitis: the effect of Levocetirizine treatment

Nermina Arifhodžić, Fadia Mahmoud, Reem Ameen, Rana Al-Awadhi


There is considerable evidence that several novel H1 antihistaminespossess anti-allergic/ anti-inflammatory properties,through inhibition of leukocyte activation. Levocetirizin andother H1 antihistamines are considered central to the treatmentof atopic dermatitis (AD) associated pruritis; howeverthere is a lack of studies of possible anti-inflammatoryeffect of these drugs in children with AD. In this study, weinvestigated the lymphocyte sub-population profile in theperipheral blood of 15 children with AD at baseline and followingtwo weeks of levocetirizine treatment. The clinicalsymptoms and flow cytometric analysis of the percentageexpression of CD4+CD25+ subsets on T cells, as well as expressionof the adhesion molecules; CD4+CD54+ (ICAM-I)and CD4+CD62+ (L-Selectin) on T cells were evaluated. Thechildren exhibited a reduction in the percentages of the eosinophilcount (p<0.05) as well as major clinical symptoms,itching/ scratching (p<0.05) and the subsequent bleeding oflesions (p<0.05); however the total symptom score was notsignificantly changed. A significant increase was observed inCD4+CD25hi Treg cells while CD4+CD54+ (ICAM-I) cellswere significantly decreased, and no significant change wasobserved in other populations. Reduction of CD4+CD54+may be associated with suppression of IgE production andhence reduced mast cell recruitment into the inflammatorysites, on the other hand; expansion of CD4+CD25hi indicatesthat Treg-mediated host immune defenses are augmented.Our study suggests the potential of the anti-inflammatory effectsof levocetirizine in allergic inflammation.


Dermatitis, Treg cells, Adhesion molecules, Levocetirizine.

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Allam, JP, Novak N. The pathophysiology of atopic eczema Clin Exp Dermatol. 2006;31(1):89-93.

Jenerowicz D, Czarnecka-Operacz M, Silny W. Selected eosinophyl proteins as a marker of inflammation in atopic dermatitis patients. Acta Dermatol Croat. 2006;14(2):73-80.

Leung DYM, Bieber T. Atopic dermatitis. The Lancet. 2003;361:151-60.

Hanifin JM, Rajka G. Diagnostic feature of atopic dernmatitis. Acta Dermatovenerologica. 1980;114 (Suppl 114):87-92.

Jenerowic D, Czarnecka –Operatcz Msilnv W. Selected eosinophil protein asa marker of inflammation in atopic deramatitis patients. Acta Dermattovenerol Croat. 2006;14:(2):73-80.

Shimada Y, Hasegava M, Kaburagi Y, Hamagushi Y, at al. L selectin or ICAM1 deficiency reduce an immediate type hypersensitivity response by preventing mast cells recruitment in repeated elicitation of contact hypersensitivity. J Immunol. 2003; 15;170(8):4325-34.

Lurzius-Spencer M, Halone M, Lohman IC, Martinez FD, Wright AL. Prenatal factors associated with the development of eczema in the first year of life. Ped Allergy and Immunol. 2005;16:19-26.

Henino A, Vocanson M,Toussaint Y, Rodet K et al. Skin infiltrating CD8+T cells initiate Atopic Dermatitis lesion. J Immunol. 2007;178(9):5571-7.

Shi H-Z Qin X-J. CD4+CD25+regulatory T lymfocites in allergy and asthma. Allergy. 2005;60:986-95.

Shwarz RH. Natural regulatory T cels and self tolerance. Nat Immunol. 2005;6:327-30.

Umetsu DT, Akbary O, De Kruy. RH. Regulatory T cells control development of allergic diseases and asthma. JACI. 2003;112:480-7.

Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, et al. Relation of CD4CD25 regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet. 2004;363:608-15.

Walker MR, Kasprowicz DJ, Gersuk VH, Van Landeghen M, Buckner JH, Ziegler SF. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4CD25- T cells. J Clin Invest. 2003;112:1437-43.

Reefer AJ, Satinover SM, Solga MD, Lannigan JA, Nguyen JT, Wilson BB, Woodfolk JA. Analysis of CD25hiCD4+ “regulatory” T-cell subtypes in atopic dermatitis reveals a novel T(H)2-like population. J Allergy Clin Immunol. 2008;121(2):415-22.

Springer TA. Adhesion receptors of the immune system. Nature. 1990;346:425-34.

Wegner CD, Gundel RH, Reilly P, Haynes N, Letts LG, Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science. 1990;247: 456-9.

Kojima T, Ohno A, Aoki T, Hayashi N, Kobayashi Y. Circulation ICAM-1 levels in children with atopic dermatitis. Ann Allergy. 1994;73:351–5.

Hashimoto S, Imai K, Kobayashi T, et al. Elevated levels of soluble ICAM-1 in sera from patients with bronchial asthma. Allergy. 1993;48:370–2.

Chihara J, Yamamoto T, Kurachi D, Nakajima S. Soluble ICAM-1 in sputum of patients with bronchial asthma. Lancet. 1994;343:1108.

Ohashi Y, Nakai Y, Tanaka A, Kakinoki Y, Washio Y. Soluble adhesion molecules in middle ear effusions from patients with chronic otitis media with effusion. Clin Otolaryngol Allied Sci.


Caproni M, Volpi W, Giomi B, Torchia D, Del Bianco E, Fabbri P. Cellular adhesion molecules in chronic urticaria: modulation of serum levels occurs during levocetirizine treatment. Br J Dermatol. 2006;155:1270-4.

Traddi-Hoffmann C, Munster I, Ring J, Behrendt H. Impact of desloratadine in and loratadine on the crosstalk between human keratinocytes and leucocites: Implication for anti-inflammatory activities of antihistamines. Int Arch Allergy Immunol. 2006;4:315-20.

Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy. 2002;32:489–98.

Walsh GM. Levocetirizine: an update. Curr Med Chem. 2006;13(22):2711-5.

Dieogen T. Long term treatment with cetirizin of infants with atopic dermatitis: a multi country, double blind randomized, placebo-controled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol. 2002;13:278-86.

Leung DYM, Nicklas RA, Li JT, Bernstein L, Blessing-Moore J, Boguniewicz M, et al. Disease management of atopic dermatitis: an updated practice parameter. Annals of Allergy, Asthma & Immunology. 2004;93(3); S1-S21.

Sedgwick JB, BusseWW. Inhibitory effect of Cetirizine on cytokine-enhanced in vitro eosinophyl durvival. Ann Allergy Asthma Immunol. 1997;78:581-5.

Lokey RF, Widlitz MD, Mitchell DQ et al. Comparative study of cetirizine and terfenadine versus placebo in the symptomatic management of seasonal allergic rhinitis.Ann Allergy Asthma Immunol 1996;76:448-54.

Breneman D, Bronsky EA, Bruce S, Kalivas JT, Klein GL, Roth HL, Tharp MD, Treger C, Soter N. Cetirizine and astemizole therapy for chronic idiopathic urticaria: a double-blind, placebo-controlled, comparative trial. J Am Acad Dermatol.

;33(2 Pt 1):192-8.

Gonda A, Gal I, Szanto S, Sarraj B, Hunyadi J, Mikecz K, Glant TT. CD44 but not I selectin is critically involved in leucocite migration int skin in a murine model of allergic dermatitis. Exp

Dermatol. 2005;14:700-8.

Albanezi C, Pastore E, Fanales-Belasio E, Girolomoni G. Cetirizine and hydrocortisone differentially regulate ICAM 1 expression and chmokine release in cultured human keratinocytes. Clin Exper Allergy.1998;28:101-9.

Wu P, Mitchel S, Walsh GM. A new antihistamine levocetirizine inhibits eosinohil adhesion to vascular cell adhesion molecule-1 under flow conditions. Clin Exper Allergy. 2005;35:1073-9.

Kroegel C, Virchow JC Jr, Luttmann W, Walker C, Warner JA. Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part I). Eur Respir J. 1994;7(3):519-43.

Morgan RK, McAllister B, Cross L, Green DS, Kornfeld H, Center DM, Cruikshank WW. Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model. J Immunol. 2007;178:8081-9.

Fumagalli F, Baiardini I, Pasquali M, Compalati E, Guera L, Massacane P, Canonica GW. Anihistamines: do they work? Further well-controlled trials involving larger samples are needed. Allergy. 2004;59 (Suppl. 78):74-7.

Steeber DA, Tang ML, Green NE, Zhang XQ, Sloane JE, Tedder TF. Leukocyte entry into sites of inflammation requires overlapping interactions between the L-selectin and ICAM-1 pathways. J Immunol. 1999;163(4):2176-86.


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