ARTICLE INFO

Article Type

Original Research

Authors

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, Iran
Phone: +982188964792
Fax: +982188966310
tghazanfari@yahoo.com

Article History

Received:  June  21, 2014
Accepted:  September 3, 2014
ePublished:  November 6, 2014

BRIEF TEXT


… [1, 2] The effects of sulfur mustard on organs depend on its amount and exposure length [3]. These effects are different in different peoples and skin sensitivity to mustard gas is not the same in different parts of the skin [4, 5]. Pigmentation disorders types depend on the melanocytesinjury level; and low to moderate levels of exposure to mustard gas can lead to hyperpigmentation. Higher levels of exposure to mustard gas lead to depigmentation and scar hypotrophy [5]. … [6-15] Tissue injury and repair process can change the pigment production pattern in the skin. After inflammation, hyperpigmentation is observed in many skin disorders such as acne, eczema and contact dermatitis [16, 17]. … [18-20] Melanin and its derivatives, which play a protective role against UV rays, might have an antimicrobial effect on the wound. In the human skin, materials, produced during the melanin synthesisprocess have high oxidative and toxic effects on the bacteria, which is similar to the defense system of the plants [21, 22]. [23-28] Natural keratinocytes of man produce IL-6 in response to different external stimuli, including UV rays, IL13, IL4, IL1, PGE2, and INFγ. Signal transduction in response to different stimuli mediates through multiple molecular pathways [29-31]. During chronic inflammation, some cytotoxic cells, basophils, eosinophils, and activated mast cells produce IL-4 [32]. IL-4 affects melanogenesis process [33].

The most common delayed skin complaints in the veterans with chemical injuries are itching, irritation, dryness of skin, scars, pigment disorders (pigmentation), and cherry angioma. There are significant incidences of rash, seborrheic dermatitis, eczema, hair loss, and acne lesions [6-10]. There are different frequencies of pigment disorders. The hyperpigmentation prevalence is between 5.9 and 55% and the frequency of hypopigmentation is between 3.2 and 40% [11]. There is a 5.5 fold prevalence of hyperpigmentation in veterans with skin problems, and destruction of the basal area after chemical burn and pouring pigment into the dermis have been proposed as the cause. Increase in IL-1 and TNFα after exposure leads to secretion of melanocyte-stimulating hormone, and might affect the pigments, locally [12]. Effects of mustard gas in the basal layer of cells and reduction in glutathione or other intracellular thiols, which lead to increase in tyrosinase activity, might result in hyperpigmentation [12]. Despite the fact that the accurate mechanisms of pigmentation due to wound are not well known, the activity of the melanocytes due to inflammatory mediators and free radicals of the released oxygen from the injured skin might contribute to its development [34].

The aim of this study was to investigate the association between IL-6 and IL-4 and pigment disorders in chemically-injured veterans exposed to mustard gas.

This is a part of the Sardasht cohort study.

Persons with mustard gas exposure (chemically-injured veterans of Sardasht City, Iran) and healthy persons (from Rabat City, Iran) were studied.

The subjects were similar in terms of age, body mass index, and marital status. Sardasht and Rabat cities were very similar to each other in geographic location, climate, customs, and nutrition. 500 subjects including 372 people exposed to mustard gas and 128 people as control group were studied. Results of 343 persons from “exposure group” and 124 persons from “control group” were included for IL-6. Results of 341persons from “exposure group” and 122 persons from “control group” were included for IL-4 [1]. Systematic random sampling was done.

“Exposure” and “control” groups were divided, based on presence or absence of pigment disorders in the form of increase or decrease in pigments (hyperpigmentation and hypopigmentation). 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 5minand the serum was separated. Serum levels of IL-4 and IL-6 were measured using ELISA sandwich and kit (R&D: USA) and was determined by ELISA reading apparatus (FLOW: USA). Mann-Whitney test was used to compare the serum levels of cytokines in the groups.

55 persons (15.5%) from “exposure” and 6 persons (4.7%) from “control” groups had hyperpigmentation disorder. 20 persons (5.2%) from “exposure” and 2 persons (1.6%) from “control” groups had hypopigmentation disorder.There was no difference in the mean serum levels of IL-6 in “exposure” group with and without hyperpigmentation disorder. There was no significant difference in the mean serum levels of IL-6 in “exposure” group with and without hypopigmentation disorder. Nevertheless, IL-6 serum level in veterans without hypopigmentation was lower than “control” group (Table 1).There was no significant difference between mean serum levels of IL-4 in “exposure” group with and without hyperpigmentation disorder. There was significant difference between mean serum levels of IL-4 in “exposure” group with and without hypopigmentation disorder; and in “exposure” group with hypopigmentation, there was more serum levels than the group without such disorder (Table 2).

Comparison between serum levels of IL-4 in “control” and “exposure” groups with and without pigment disorders, showed an increase in the cytokine in disorder conditions in “exposure” group. However, onlythere was a significant difference in hypopigmentation group. IL-4 affects Melanogenesis process [32, 33]. … [35-37] IL-4 directly inhibits Melanin synthesis in Keratinocyte of Melanocytes via Jak2/STAT6 Signaling Pathway [38].… [40]

The roles of immune factors, such as IL-4 and IL-6 ought to be included in the explanation of correlation between mustard gas exposure and pigment disorders.

Non-declared

Changes in serum levels of IL-4 and IL-6 may be involved in hypopigmentation.

The researchers feel grateful to all the participants.

Non-declared

Non-declared

The study was funded by Martyrs and Veteran Foundation, Ministry of Health and Medical Education (Iran), Shahed University, and Janbazan Medical and Engineering Research Center.

TABLES and CHARTS

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CITIATION LINKS

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