@2024 Afarand., IRAN
ISSN: 2008-2630 Iranian Journal of War & Public Health 2014;6(5):215-220
ISSN: 2008-2630 Iranian Journal of War & Public Health 2014;6(5):215-220
Relationship of Interleukin-4 and Interleukin-6 with Pigmentation Disorders in Sardasht Sulfur Mustard- Exposed Veterans; 20 Years after Exposure
ARTICLE INFO
Article Type
Original ResearchAuthors
Askari N (1)Ghazanfari T (*)
Jalaie Sh (2)
Davoudi S.M (3)
Soroush M.R (4)
(*) Immunoregulation Research Center, Shahed University, Tehran, Iran
(1) Biology Department, Sciences Faculty, Shahid Bahonar University of Kerman, Kerman, Iran
(2) Physiotherapy Department, Rehabilitation Faculty, Tehran University of Medical Sciences, Tehran, Iran
(3) Dermatology Department, Medicine Faculty, Baqiyatallah University of Medical Sciences, Tehran, Iran
(4) Janbazan Medical and Engineering Research Center, Tehran, Iran
Correspondence
Address: Immunoregulation Research Center, 4th floor, Research Center Building of Shahed University, No. 1471, Corner of Mehr Alley, North Karegar Street, Tehran, IranPhone: +982188964792
Fax: +982188966310
tghazanfari@yahoo.com
Article History
Received: June 21, 2014Accepted: September 3, 2014
ePublished: November 6, 2014
ABSTRACT
Aims
Pigmentation disorders are one of the main skin problems due to mustard gas exposure
in chemically-injured veterans. The aim of this study as part of the Sardasht cohort study was
to investigate the association between IL-6 and IL-4 and pigment disorders in chemicallyinjured
veterans exposed to mustard gas.
Materials & Methods In this study, 500 subjects including 372 people exposed to mustard gas and 128 people as control group were studied. Systematic random sampling was done. 2cc of peripheral blood of each subject was taken and the blood was allowed to be clotted at the room temperature (37°C). Tubes containing the clotted blood centrifuged for 5min and the serum was separated. Serum levels of IL-4 and IL-6 were measured using the ELISA sandwich and kit was determined using ELISA reading apparatus. Mann-Whitney test was used to compare the serum levels of cytokines in the studied groups.
Findings Serum levels of IL-6 in veterans with and without reduction or increase in pigmentation disorders showed no significant difference. But compared with control group, there was a significant reduction in veterans without hypopigmentation disorder, while there was no significant difference between control group veterans with hypopigmentation disorder. Serum levels of IL-4 significantly increased in veterans with hypopigmentation disorder compared with veterans without the disorder.
Conclusion Changes in serum levels of Il-4 and Il-6 may be involved in hypopigmentation.
Materials & Methods In this study, 500 subjects including 372 people exposed to mustard gas and 128 people as control group were studied. Systematic random sampling was done. 2cc of peripheral blood of each subject was taken and the blood was allowed to be clotted at the room temperature (37°C). Tubes containing the clotted blood centrifuged for 5min and the serum was separated. Serum levels of IL-4 and IL-6 were measured using the ELISA sandwich and kit was determined using ELISA reading apparatus. Mann-Whitney test was used to compare the serum levels of cytokines in the studied groups.
Findings Serum levels of IL-6 in veterans with and without reduction or increase in pigmentation disorders showed no significant difference. But compared with control group, there was a significant reduction in veterans without hypopigmentation disorder, while there was no significant difference between control group veterans with hypopigmentation disorder. Serum levels of IL-4 significantly increased in veterans with hypopigmentation disorder compared with veterans without the disorder.
Conclusion Changes in serum levels of Il-4 and Il-6 may be involved in hypopigmentation.
CITATION LINKS
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[2]Balali-Mood M, Hefazi M. Comparison of early and late toxic effects of sulfur mustard in Iranian veterans. Basic Clin Pharmacol Toxicol. 2006;99(4):273-82.
[3]Paromov V, Suntres Z, Smith M, Stone WL. Sulfur mustard toxicity following dermal exposure. J Burns Wounds. 2007;7: e7.
[4]Institute of Medicine (Author), Committee on the Institute of Medicine (Author), David P. Rall. Veterans at risk, the health effects of mustard gas and lewisite. 1st ed. Washington: National Academy Press; 1993.
[5]Mortazavi H, Raziee M, Emadi SN, Nakhai MJ, Soroush MR, Noormohammad pour P, et al. Skin lesions in 800 Iranian victims of mustard gas, 14-20 years after exposure. Iran J Dermatol. 2005;8(31):177-89. [Persian]
[6]Moin A, Ghazanfari T, Davoudi SM, Emadi SN, Panahi Y, Mohammad Hassan Z, et al. Long-term skin findings of sulfur mustard exposure on the civilians of Sardasht, Iran. Toxin Rev. 2009;28(1):24-9.
[7]Momeni AZ, Enshaeih S, Meghadi M, Amindjavaheri M. Skin manifestations of mustard gas. A clinical study of 535 patients exposed to mustard gas. Arch Dermatol. 1992;128(6):775-80.
[8]Naraghi ZS, Mansouri P, Mortazavi M. A clinicopathological study on acute cutaneous lesions induced by sulfur mustard gas (yperite). Eur J Dermatol. 2005;15(3):140-5.
[9]Hefazi M, Maleki M, Mahmoudi M, Tabatabaee A, Balali-Mood M. Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16-20 years after exposure. Int J Dermatol. 2006;45(9):1025-31.
[10]Emadi SN, Mortazavi M, Mortazavi H. Late cutaneous manifestations 14 to 20 years after wartime exposure to sulfur mustard gas: A long term investigation. Arch Dermatol. 2008;144(8):1059-61.
[11]Moin A, Davoodi SM. A review of acute and chronic skin complications of sulfur mustard exposure. Dermatol Cosmetic. 2011;2(1):35-46.
[12]Fekri AR, Janghorbani M. Late cutaneous complication in chemical warfare victims in Kerman province. J Kerman Univ Med Sci. 1995;2(3):108-19.
[13]Ito S, Wakamatsu K. Chemistry of mixed melanogenesis-pivotal roles of dopaquinone. Photochem Photobiol. 2008;84(3):582-92
[14]Costin GE, Hearing VJ. Human skin pigmentation: Melanocytes modulate skin color in response to stress. FASEB J. 2007;21(4):976-94.
[15]Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature. 2007;445:843-50.
[16]King R, Googe PB, Page RN, Mihm MC Jr. Melanocytic lesions associated with dermatofibromas: a spectrum of lesions ranging from junctional nevus to malignant melanoma in situ. Mod Pathol. 2005;18(8):1043-7.
[17]Cardinali G, Kovacs D, Picardo M. Mechanisms underlying post-inflammatory hyperpigmentation: Lessons from solar lentigo. Ann Dermatol Venereol. 2012;139(Suppl 3):96-101
[18]Lévesque M, Feng Y, Jones RA, Martin P. Inflammation drives wound hyperpigmentation in zebrafish by recruiting pigment cells to sites of tissue damage. Dis Model Mech. 2013;6(2):508-15.
[19]Bidla G, Dushay MS, Theopold U. Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger. J Cell Sci. 2007;120(Pt 7):1209-15.
[20]Galko MJ, Krasnow MA. Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol. 2004;2(8):e239.
[21]Chisholm ST1, Coaker G, Day B, Staskawicz BJ. Host-microbe interactions: Shaping the evolution of the plant immune response. Cell. 2006;124(4):803-14.
[22]Mackintosh JA. The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin. J Theor Biol. 2001;211(2):101-13.
[23]Sugata K, Kitahara T, Takema Y. Changes of human skin in subepidermal wound healing process. Skin Res Technol. 2008;14(4):436-9.
[24]Scott G, Leopardi S, Printup S, Malhi N, Seiberg M, Lapoint R. Proteinase-activated receptor-2 stimulates prostaglandin production in keratinocytes: analysis of prostaglandin receptors on human melanocytes and effects of PGE2 and PGF2alpha on melanocyte dendricity. J Invest Dermatol. 2004;122(5):1214-24.
[25]Ford-Hutchinson AW, Rackman A. Leukotrienes as mediators of skin inflammation. Br J Dermatol. 1983;109(suppl 25):26-9.
[26]Fogh K, Herlin T, Kragballe K. Eicosanoids in skin of patients with atopic dermatitis: Prostaglandin E2 and leukotriene B4 are present in biologically active concentrations. J Allergy Clin Immunol. 1989;83(2 Pt 1):450-5.
[27]Wang S, Zhou M, Lin F, Liu D, Hong W, Lu L, et al. Interferon-γ induces senescence in normal human melanocytes. PLoS One. 2014;28;9(3):e93232.
[28]Monfrecola G, Lembo S, Cantelli M, Ciaglia E, Scarpato L, Fabbrocini G, et al. The effect of visible blue light on the differentiation of dendritic cells in vitro. Biochimie. 2014;101:252-5
[29]Derocq JM, Segui M, Poinot-Chazel C, Minty A, Caput D, Ferrara P, et al. Interleukin-13 stimulates interleukin-6 production by human keratinocytes. Similarity with interleukin-4. FEBS Lett. 1994;343(1):32-6.
[30]Chung JH, Youn SH, Koh WS, Eun HC, Cho KH, Park KC, et al. Ultraviolet B irradiation-enhanced interleukin (IL)-6 production and mRNA expression are mediated by IL-1 alpha in cultured human keratinocytes. J Invest Dermatol. 1996;106(4):715-20.
[31]Teunissen MB, Koomen CW, de Waal Malefyt R, Wierenga EA, Bos JD. Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol. 1998;111(4):645-9.
[32]Barata LT, Ying S, Meng Q, Barkans J, Rajakulasingam K, Durham SR, Kay AB. IL-4- and IL-5-positive T lymphocytes, eosinophils, and mast cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Allergy Clin Immunol. 1998;101(2 Pt 1):222-30.
[33]Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004;84(4):1155-228.
[34]Ortonne JP, Bissett DL. Latest insights into skin hyperpigmentation. J Investig Dermatol Symp Proc. 2008;13(1):10-4.
[35]
[36]Choi H, Ahn S, Lee BG, Chang I, Hwang JS. Inhibition of skin pigmentation by an extract of Lepidium apetalum and its possible implication in IL-6 mediated signaling. Pigment Cell Res. 2005;18(6):439-46.
[37]Vachtenheim J, Borovanský J. "Transcription physiology" of pigment formation in melanocytes: Central role of MITF. Exp Dermatol. 2010;19(7):617-27.
[38]Turksen K1, Kupper T, Degenstein L, Williams I, Fuchs E. Interleukin 6: insights to its function in skin by overexpression in transgenic mice. Proc Natl Acad Sci U S A. 1992;89(11):5068-72.
[39]Choi H, Choi H, Han J, Jin SH, Park JY, Shin DW, et al. IL-4 inhibits the melanogenesis of normal human melanocytes through the JAK2-STAT6 signaling pathway. J Invest Dermatol. 2013;133(2):528-36.
[40]Boguniewicz M, Leung DY. Atopic dermatitis: A disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-46.
[41]Synnerstad I, Nilsson L, Fredrikson M, Rosdahl I. Fewer melanocytic nevi found in children with active atopic dermatitis than in children without dermatitis. Arch Dermatol. 2004;140(12):1471-5.
[2]Balali-Mood M, Hefazi M. Comparison of early and late toxic effects of sulfur mustard in Iranian veterans. Basic Clin Pharmacol Toxicol. 2006;99(4):273-82.
[3]Paromov V, Suntres Z, Smith M, Stone WL. Sulfur mustard toxicity following dermal exposure. J Burns Wounds. 2007;7: e7.
[4]Institute of Medicine (Author), Committee on the Institute of Medicine (Author), David P. Rall. Veterans at risk, the health effects of mustard gas and lewisite. 1st ed. Washington: National Academy Press; 1993.
[5]Mortazavi H, Raziee M, Emadi SN, Nakhai MJ, Soroush MR, Noormohammad pour P, et al. Skin lesions in 800 Iranian victims of mustard gas, 14-20 years after exposure. Iran J Dermatol. 2005;8(31):177-89. [Persian]
[6]Moin A, Ghazanfari T, Davoudi SM, Emadi SN, Panahi Y, Mohammad Hassan Z, et al. Long-term skin findings of sulfur mustard exposure on the civilians of Sardasht, Iran. Toxin Rev. 2009;28(1):24-9.
[7]Momeni AZ, Enshaeih S, Meghadi M, Amindjavaheri M. Skin manifestations of mustard gas. A clinical study of 535 patients exposed to mustard gas. Arch Dermatol. 1992;128(6):775-80.
[8]Naraghi ZS, Mansouri P, Mortazavi M. A clinicopathological study on acute cutaneous lesions induced by sulfur mustard gas (yperite). Eur J Dermatol. 2005;15(3):140-5.
[9]Hefazi M, Maleki M, Mahmoudi M, Tabatabaee A, Balali-Mood M. Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16-20 years after exposure. Int J Dermatol. 2006;45(9):1025-31.
[10]Emadi SN, Mortazavi M, Mortazavi H. Late cutaneous manifestations 14 to 20 years after wartime exposure to sulfur mustard gas: A long term investigation. Arch Dermatol. 2008;144(8):1059-61.
[11]Moin A, Davoodi SM. A review of acute and chronic skin complications of sulfur mustard exposure. Dermatol Cosmetic. 2011;2(1):35-46.
[12]Fekri AR, Janghorbani M. Late cutaneous complication in chemical warfare victims in Kerman province. J Kerman Univ Med Sci. 1995;2(3):108-19.
[13]Ito S, Wakamatsu K. Chemistry of mixed melanogenesis-pivotal roles of dopaquinone. Photochem Photobiol. 2008;84(3):582-92
[14]Costin GE, Hearing VJ. Human skin pigmentation: Melanocytes modulate skin color in response to stress. FASEB J. 2007;21(4):976-94.
[15]Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature. 2007;445:843-50.
[16]King R, Googe PB, Page RN, Mihm MC Jr. Melanocytic lesions associated with dermatofibromas: a spectrum of lesions ranging from junctional nevus to malignant melanoma in situ. Mod Pathol. 2005;18(8):1043-7.
[17]Cardinali G, Kovacs D, Picardo M. Mechanisms underlying post-inflammatory hyperpigmentation: Lessons from solar lentigo. Ann Dermatol Venereol. 2012;139(Suppl 3):96-101
[18]Lévesque M, Feng Y, Jones RA, Martin P. Inflammation drives wound hyperpigmentation in zebrafish by recruiting pigment cells to sites of tissue damage. Dis Model Mech. 2013;6(2):508-15.
[19]Bidla G, Dushay MS, Theopold U. Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger. J Cell Sci. 2007;120(Pt 7):1209-15.
[20]Galko MJ, Krasnow MA. Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol. 2004;2(8):e239.
[21]Chisholm ST1, Coaker G, Day B, Staskawicz BJ. Host-microbe interactions: Shaping the evolution of the plant immune response. Cell. 2006;124(4):803-14.
[22]Mackintosh JA. The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin. J Theor Biol. 2001;211(2):101-13.
[23]Sugata K, Kitahara T, Takema Y. Changes of human skin in subepidermal wound healing process. Skin Res Technol. 2008;14(4):436-9.
[24]Scott G, Leopardi S, Printup S, Malhi N, Seiberg M, Lapoint R. Proteinase-activated receptor-2 stimulates prostaglandin production in keratinocytes: analysis of prostaglandin receptors on human melanocytes and effects of PGE2 and PGF2alpha on melanocyte dendricity. J Invest Dermatol. 2004;122(5):1214-24.
[25]Ford-Hutchinson AW, Rackman A. Leukotrienes as mediators of skin inflammation. Br J Dermatol. 1983;109(suppl 25):26-9.
[26]Fogh K, Herlin T, Kragballe K. Eicosanoids in skin of patients with atopic dermatitis: Prostaglandin E2 and leukotriene B4 are present in biologically active concentrations. J Allergy Clin Immunol. 1989;83(2 Pt 1):450-5.
[27]Wang S, Zhou M, Lin F, Liu D, Hong W, Lu L, et al. Interferon-γ induces senescence in normal human melanocytes. PLoS One. 2014;28;9(3):e93232.
[28]Monfrecola G, Lembo S, Cantelli M, Ciaglia E, Scarpato L, Fabbrocini G, et al. The effect of visible blue light on the differentiation of dendritic cells in vitro. Biochimie. 2014;101:252-5
[29]Derocq JM, Segui M, Poinot-Chazel C, Minty A, Caput D, Ferrara P, et al. Interleukin-13 stimulates interleukin-6 production by human keratinocytes. Similarity with interleukin-4. FEBS Lett. 1994;343(1):32-6.
[30]Chung JH, Youn SH, Koh WS, Eun HC, Cho KH, Park KC, et al. Ultraviolet B irradiation-enhanced interleukin (IL)-6 production and mRNA expression are mediated by IL-1 alpha in cultured human keratinocytes. J Invest Dermatol. 1996;106(4):715-20.
[31]Teunissen MB, Koomen CW, de Waal Malefyt R, Wierenga EA, Bos JD. Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol. 1998;111(4):645-9.
[32]Barata LT, Ying S, Meng Q, Barkans J, Rajakulasingam K, Durham SR, Kay AB. IL-4- and IL-5-positive T lymphocytes, eosinophils, and mast cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Allergy Clin Immunol. 1998;101(2 Pt 1):222-30.
[33]Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004;84(4):1155-228.
[34]Ortonne JP, Bissett DL. Latest insights into skin hyperpigmentation. J Investig Dermatol Symp Proc. 2008;13(1):10-4.
[35]
[36]Choi H, Ahn S, Lee BG, Chang I, Hwang JS. Inhibition of skin pigmentation by an extract of Lepidium apetalum and its possible implication in IL-6 mediated signaling. Pigment Cell Res. 2005;18(6):439-46.
[37]Vachtenheim J, Borovanský J. "Transcription physiology" of pigment formation in melanocytes: Central role of MITF. Exp Dermatol. 2010;19(7):617-27.
[38]Turksen K1, Kupper T, Degenstein L, Williams I, Fuchs E. Interleukin 6: insights to its function in skin by overexpression in transgenic mice. Proc Natl Acad Sci U S A. 1992;89(11):5068-72.
[39]Choi H, Choi H, Han J, Jin SH, Park JY, Shin DW, et al. IL-4 inhibits the melanogenesis of normal human melanocytes through the JAK2-STAT6 signaling pathway. J Invest Dermatol. 2013;133(2):528-36.
[40]Boguniewicz M, Leung DY. Atopic dermatitis: A disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-46.
[41]Synnerstad I, Nilsson L, Fredrikson M, Rosdahl I. Fewer melanocytic nevi found in children with active atopic dermatitis than in children without dermatitis. Arch Dermatol. 2004;140(12):1471-5.