Metal Allergens Research Articles

Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2

Development of contact allergy requires cooperation of adaptive and innate immunity. Ni(2+) stimulates innate immunity via TLR4/MD2, the bacterial LPS receptor. This likely involves receptor dimerization, but direct proof is pending and it is unclear if related haptens share this mechanism. We reveal Co(2+) as second metal stimulating TLR4 and confirm necessity of H456/H458 therein. Experiments with a new TLR4 dimerization mutant established dimerization as a mechanism of metal- and LPS-induced TLR4 activation. Yet, in interaction studies only LPS- but not metal-induced dimerization required MD2. Consistently, soluble TLR4 expressed without MD2 inhibited metal- but not LPS-induced responses, opening new therapeutic perspectives.

Cross-reactivity among some metals in a murine metal allergy model

Information concerning cross-reactivity among metal allergens is scarce. We previously devised a murine metal allergy model using lipopolysaccharide (LPS) as an adjuvant. LPS reduces the minimum allergy-inducing concentration (MAIC) of metals at both the sensitization and the elicitation steps. Here, we examined allergic cross-reactivity among some metals in this murine model, and compared the effects of ultrapure (99·99% or more) and low purity (93-99%) metal salts. A mixture of a metal salt and Escherichia coli LPS was injected intraperitoneally into BALB/c mice (0·25 mL per mouse). Ten days later, metal salts (with or without LPS) were challenged to ear pinnas (20 μL per ear), and ear swelling was measured. Among the ultrapure metals tested (Ni, Pd, Co, Cr, Cu and Au), only Ni and Pd cross-reacted. In this cross-reaction, their MAICs were at the same level. Combined challenge with Ni and Pd at sub-MAICs (but not at higher concentrations) produced an additive effect. Surprisingly, mice sensitized with low purity Ni reacted to all the tested low purity metals (Ni, Pd, Co and Cr), and the low purity metals were shown to contain contaminant metals. In our model: (i) Ni and Pd (members of the same group in the periodic table of elements) cross-react with each other, (ii) this cross-reaction may depend on true and false antigens forming metal-protein complexes with similar spatial geometries, (iii) Co, Cr, Cu and Au do not cross-react with each other, (iv) in low purity materials, trace contaminant metals may be sufficient to evoke allergy, and thus (v) high purity metal salts should be considered for use in clinical patch testing.

Patch Testing with a Large Series of Metal Allergens: Findings from More Than 1,000 Patients in One Decade at Mayo Clinic

The standard allergen series used in patch testing contains metals that most commonly cause allergic contact dermatitis, but testing with additional metal allergens is warranted for select patients. To report our experience with patch testing of metals. We retrospectively analyzed outcomes of 1,112 patients suspected of having metal allergies. Patients were seen from January 1, 2000, through December 31, 2009. Patch testing was performed with 42 metal preparations (6 in the standard series, 36 in the metal series). Patch testing most commonly was performed for patients with oral disease (almost half the patients), hand dermatitis, generalized dermatitis, and dermatitis affecting the lips, legs, arms, trunk, or face. At least one positive reaction was reported for 633 patients (57%). Metals with the highest allergic patch-test reaction rates were nickel, gold, manganese, palladium, cobalt, Ticonium, mercury, beryllium, chromium, and silver. Metals causing no allergic patch-test reactions were titanium, Vitallium, and aluminum powder. Metals with extremely low rates of allergic patch-test reactions included zinc, ferric chloride, and tin. Reaction rates varied depending on metal salt, concentration, and timing of readings. Many metals not in the standard series were associated with allergic patch-test reactions. The many questions raised by these findings, concerning patch testing with individual metals, will be the subject of future studies.

Haptenation: Chemical Reactivity and Protein Binding

Low molecular weight chemical (LMW) allergens are commonly referred to as haptens. Haptens must complex with proteins to be recognized by the immune system. The majority of occupationally related haptens are reactive, electrophilic chemicals, or are metabolized to reactive metabolites that form covalent bonds with nucleophilic centers on proteins. Nonelectrophilic protein binding may occur through disulfide exchange, coordinate covalent binding onto metal ions on metalloproteins or of metal allergens, themselves, to the major histocompatibility complex. Recent chemical reactivity kinetic studies suggest that the rate of protein binding is a major determinant of allergenic potency; however, electrophilic strength does not seem to predict the ability of a hapten to skew the response between Th1 and Th2. Modern proteomic mass spectrometry methods that allow detailed delineation of potential differences in protein binding sites may be valuable in predicting if a chemical will stimulate an immediate or delayed hypersensitivity. Chemical aspects related to both reactivity and protein-specific binding are discussed.

Metal allergen of the 21st century-a review on exposure, epidemiology and clinical manifestations of palladium allergy

Consumers are mainly exposed to palladium from jewellery and dental restorations. Palladium contact allergy is nearly always seen together with nickel allergy, as palladium and nickel tend to cross-react. We aimed to analyse the available palladium patch test data and case reports to determine whether the prevalence of palladium mono-sensitization has increased. Based on available patch test data from the period 1986-2008, a total of 10 778 patients were patch tested with palladium chloride. The median prevalence of palladium allergy was 7.8% (range <1.0-19.0%) in dermatitis patients and 7.4% (range 1.3-13.9%) in dental patients. The median prevalence of palladium mono-sensitization (defined as the presence of palladium allergy and the absence of nickel allergy) was 0.2% (range 0-1.6%) in dermatitis patients and 0.5% (range 0-7.2%) in dental patients. A slight increase in the prevalence of palladium mono-sensitization was observed over the study period. We conclude that clinically relevant palladium allergy should mainly be suspected in patients who present with allergic contact granulomas at sites of piercing, but also in patients who have clinical disease and palladium patch test reactivity without concomitant nickel reactivity. Palladium salts should be included in dental screening patch test series. Palladium use in jewellery should be limited until we know more about the risk of sensitization.

Total-body Exposure to Metal Sensitizers: Inhalation, Ingestion, and Skin Contact

O-30A6-4 Background/Aims: Exposures to sensitizing metals are a significant public and occupational health problem. Once sensitized, a person must avoid repeated exposures to specific metal(s) to prevent elicitation of adverse responses. Exposures may occur via inhalation, ingestion, and skin contact, with each pathway contributing to the total-body insult. The purpose of this study was to evaluate the solubility and absorption potential of 2 model metal allergens, cobalt, and beryllium, in the lung, gastrointestinal, and skin compartments. Methods: Solubility of cobalt and beryllium metal particles was evaluated using 1 or more biologically relevant artificial solvents: lung airway lining fluid, lung alveolar macrophage phagolysosomal fluid, gastrointestinal fluid, and skin sweat. Solubility tests provided estimates of bioaccessibility (amount available for absorption). Absorption across biological barriers was estimated using published human and animal toxicology literature. Results: Dissolution rates for cobalt metal particles, in units of g/(cm2 × day), were fastest in gastrointestinal fluid (3.7 ± 1.6 × 10 − 4) and slower in skin sweat (4.4 ± 0.4 × 10 − 5), lung alveolar macrophage phagolysosomal fluid (2.8 ± 0.8 × 10 − 5), and airway lining fluid (1.0 ± 0.3 × 10 − 5). For beryllium metal particles, dissolution rates were fastest in gastrointestinal fluid (4.1 ± 0.2 × 10 − 7) and slower in phagolysosomal fluid (1.1 ± 1.4 × 10 − 7), skin sweat (1.7 ± 0.6 × 10 − 8), and airway lining fluid (1.5 ± 0.8 × 10 − 9). Literature indicates the absorption of particulate cobalt compounds is 30% via inhalation, 3% to 50% via ingestion, and 0.024% and 3.6% via intact and abraded skin, respectively. Absorption of particulate beryllium compounds is <1% via ingestion. In the absence of inhalation and skin absorption values for particulate beryllium, levels were assumed to be similar to divalent cations such as cobalt. Conclusion: Cobalt and beryllium metal particles are soluble in biological fluids and may be absorbed via multiple exposure pathways. Based on the range of absorption values among biological compartments, systemic dose may be limited by dissolution rates.

Metal patch test results from 1990–2009

Although metals are common contact allergens, clinical findings of metal contact dermatitis have varied. Such patients have subsequently become rare in Japan as gold dermatitis caused by ear piercing or baboon syndrome by broken thermometers. To evaluate such clinical findings and to determine the frequency of metal allergy, we analyzed the results of patch testing with 18 metals from 1990-2009. Nine hundred and thirty-one patients (189 men and 742 women, mean age 39.0years [standard deviation±17.8]) were tested. Metals were applied on the back for 2days, and the results read with the International Contact Dermatitis Research Group (ICDRG) scoring system 3days after application. Reactions of + to +++ were regarded as positive. Differences of positive rates between men and women, and patients from 1990-1999 and those from 2000-2009 were analyzed with the χ(2) -test. Differences were considered significant at P<0.05. The metal to which the most patients reacted was 5% nickel sulfate (27.2%), irrespective of sex and phase. Significantly more women reacted to nickel sulfate (P<0.01), mercuric chloride (P<0.05) and gold chloride (P<0.01) than men. Significantly more patients in the 1990s reacted to palladium chloride, mercuric chloride and gold chloride (all P<0.01) than from 2000-2009. Nickel has been the most common metal allergen and mercury-sensitivity has decreased over 19years in Japan.

Patch test reactivity to metal allergens following regulatory interventions: a 33-year retrospective study

Contact allergy epidemics to chromate and nickel were addressed in Denmark in 1983 and 1990 by regulatory interventions. To evaluate whether regulatory interventions on nickel and chromate exposure have reduced the proportion of strong patch test reactions. 22 506 patients with dermatitis aged 4-99 years were patch tested with nickel sulfate, potassium dichromate, or cobalt chloride between 1977 and 2009. The proportion of 3+ reactions to nickel sulfate was reduced and almost disappeared after the mid- and late 1980s (P-trend = 0.001). Today, 1+ and 2+ nickel reactions occur equally frequent. Cobalt chloride patch test reactivity reflected the nickel development to some degree. The proportion of 3+ reactions to potassium dichromate was reduced during the 1980s (P-trend = 0.13), whereas the proportion of 2+ reactions to potassium dichromate have increased in recent years. The decrease in nickel sulfate and cobalt chloride 3+ patch test reactivity began long before the Danish nickel regulation came into effect. This could be because of research activity at the time as well as political attention in Northern Europe. The chromate content in cement regulation may have changed the epidemiology of patch test reactivity; however, in recent years, 2+ reactions to chromate have increased markedly, a development that should be carefully followed.

No association between nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow: a cross‐sectional general population study

In theory, all pigmented make-up products may contain metal allergens including nickel. Eyelid dermatitis has previously been observed among nickel allergic dermatitis patients following exposure to nickel containing mascara and eye shadow. However, an association between nickel eyelid dermatitis and nickel in make-up products remains controversial. This cross-sectional patch test study investigated whether the frequency of self-reported cosmetic dermatitis from mascara or eye shadow use was higher among nickel allergic Danish women than women without nickel allergy. In 2006, a total of 1843 18-69 year old women completed a postal questionnaire including questions on cosmetic dermatitis and were patch tested with nickel sulphate. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The prevalence of nickel allergy was similar among women who reported cosmetic dermatitis from eye shadow or mascara and among women who did not report such symptoms. Cosmetic dermatitis was positively associated with self-reported atopic dermatitis and age. Overall, no association between having nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow use was found in the general population. This does not exclude a causal relationship in selected cases.

Oxidation of Cell Surface Thiol Groups by Contact Sensitizers Triggers the Maturation of Dendritic Cells

p38 mitogen-activated protein kinase (MAPK) has a crucial role in the maturation of dendritic cells (DCs) by sensitizers. Recently, it has been reported that the oxidation of cell surface thiols by an exogenous impermeant thiol oxidizer can phosphorylate p38 MAPK. In this study, we examined whether sensitizers oxidize cell surface thiols of monocyte-derived DCs (MoDCs). When cell surface thiols were quantified by flow cytometry using Alexa fluor maleimide, all the sensitizers that we examined decreased cell surface thiols on MoDCs. To examine the effects of decreased cell surface thiols by sensitizers on DC maturation, we analyzed the effects of an impermeant thiol oxidizer, o-phenanthroline copper complex (CuPhen). The treatment of MoDCs with CuPhen decreased cell surface thiols, phosphorylated p38 MAPK, and induced MoDC maturation, that is, the augmentation of CD83, CD86, HLA-DR, and IL-8 mRNA, as well as the downregulation of aquaporin-3 mRNA. The augmentation of CD86 was significantly suppressed when MoDCs were pretreated with N-acetyl-L-cystein or treated with SB203580. Finally, we showed that epicutaneous application of 2,4-dinitrochlorobenzene on mouse skin significantly decreased cell surface thiols of Langerhans cells in vivo. These data suggest that the oxidation of cell surface thiols has some role in triggering DC maturation by sensitizers.

Contact sensitization to metals in Taiwan

Correlation of several patient factors with contact sensitization to nickel, cobalt, chromate, and other metal allergens has not been reviewed in the Taiwanese population. A retrospective analysis was performed to define the characteristics of patients with positive patch tests to metals in a tertiary referral medical centre between 1978 and 2003. Patch test data of 3559 patients at a medical centre in Taiwan from 1978 to 2003 were retrospectively analysed. Contact sensitization to metals was defined as a positive reaction to at least one of the metal substances in the patch test series. Chi-squared test, Fisher's exact test, and multivariate logistic regression were used for statistical analysis. Female patients were more likely to have contact sensitization to metal allergens except chromate or mercurochrome. Patients who reacted to chromate were more likely to be male, with an occupational correlation, older age, and a site of predilection towards the extremities. Within the first and sixth decades of age, thimerosal and chromate were the leading causes of metal contact sensitization, respectively. Nickel was the major metal sensitizer among the other age groups. Several patient factors were characterized related to metal sensitization in the Taiwanese population. The sources of exposure were further discussed.

Metal Allergens of Growing Significance: Epidemiology, Immunotoxicology, Strategies for Testing and Prevention

Metal-induced allergic contact dermatitis (ACD) is expressed in a wide range of cutaneous reactions following dermal and systemic exposure to products such as cosmetics and tattoos, detergents, jewellery and piercing, leather tanning, articular prostheses and dental implants. Apart from the well known significance of nickel in developing ACD, other metals such as aluminium, beryllium, chromium, cobalt, copper, gold, iridium, mercury, palladium, platinum, rhodium and titanium represented emerging causes of skin hypersensitivity. Despite the European Union directives that limit the total nickel content in jewellery alloys, the water soluble chromium (VI) in cement, and metals banned in cosmetics, the diffusion of metal-induced ACD remained quite high. On this basis, a review on the epidemiology of metal allergens, the types of exposure, the skin penetration, the immune response, and the protein interaction is motivated. Moreover, in vivo and in vitro tests for the identification and potency of skin-sensitizing metals are here reviewed in a risk assessment framework for the protection of consumer's health. Avenues for ACD prevention and therapy such as observance of maximum allowable metal levels, optimization of metallurgic characteristics, efficacy of chelating agents and personal protection are also discussed.

Hypersensitive pneumonitis caused by exposure of metal allergens

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Pathomorphology of bronchopulmonary diseases in workers exposed to colored metal aerosols

Etiopathogenic features and diagnostic criteria of occupational diseases studying in workers engaged in colored metallurgy have been given in the paper. Polyvalent sensitization to metal allergens (nickel, chrome, beryllium, manganese) was found. A toxic effect of nickel on DNA was shown that could be used as a biomarker of exposure for biological monitoring in colored metallurgy workers. Biochemical investigations determined the main pathogenic mechanisms underlying pathomorphology of bronchopulmonary diseases caused by the exposure of colored metals, such as activation of lipid peroxidation, "proteolysis – antiproteolysis" imbalance, growing significance of infection. This is the first study demonstrating clinical and biochemical parallels between characteristics of development and course of respiratory pathology caused by the exposure of colored metals. Infectious, inflammatory, toxico-allergic, and destructive processes predominated in this pathology. Preventive and rehabilitation strategies have been developed.

Patch Test Results with Metals and Meteorological Conditions

Background: Nickel, cobalt and chromium are some of the most common causes of type IV sensitizations and subsequent allergic contact dermatitis. Accurate diagnosis of contact sensitization to these metal salts is made possible through standardized patch testing; however, patch tests with metal allergens may be influenced by meteorological conditions at the time of testing. We aimed to investigate how patch test reactions to these metals relate to outdoor temperature and humidity at the time of testing. Methods: Clinical patch test results from 61,435 patients tested at Austrian and German dermatology departments participating in a contact sensitization surveillance network (www.ivdk.org) from 1993 through 2001 were evaluated with weather data measured near the testing location and at the time of testing. Test reactions and ambient temperature and humidity were examined with multinomial logistic regression models. Results: The odds of irritant and doubtful reactions to all 3 ionized metals increased during cold/arid conditions, and the odds of weak allergic (positive) reactions to nickel and cobalt also increased during cold/dry weather. Strong allergic reactions were essentially independent of weather conditions. Conclusions: The increase in irritant and doubtful reactions coinciding with decreasing temperature and humidity may be the result of an overall increase in skin irritation brought about by these ambient conditions. The observed increases in erythematous and infiltrated (‘weak allergic’) reactions may be due to doubtful reactions increasing in intensity and being (falsely) classified as positive during colder and drier conditions.

A new dendritic cell type suitable as sentinel of contact allergens

Establishing of alternatives to animal tests is ethically desirable and gains in importance in context of new European Union regulations such as REACH. We have refined our new in vitro assay for prediction of the sensitizing potency of xenobiotics. Monocytes cocultured with primary human keratinocytes develop to a novel class of in vitro generated dendritic cells after treatment with transforming growth factor beta and Interleukin-4 in serum-free medium. These dendritic cell-related cells (DCrc) are the key players in the loose-fit coculture-based sensitization assay (LCSA). Assay duration and cytokine consumption could be cut down without impairing the assay's functionality. DCrc showed a dose-dependent upregulation of CD86 after treatment with the contact allergens 2,4,6-trinitrobenzenesulfonic acid, the prohapten isoeugenol, and alpha-hexyl cinnamic aldehyde. The metal allergens nickel and cobalt could be detected by measuring Interleukin-6 and macrophage inflammatory protein 1-beta (MIP-1beta, CCL-4) in coculture supernatants. The irritant zinc elicited no reaction. Lipopolysaccharide produced upregulation of CD86, IL-6 and MIP-1beta. Determination of tolerable concentrations of an allergen in consumer products requires a widely accepted sharp quantitative assay. Animal-based assays do not meet this requirement. The LCSA provides dose–response information, thereby allowing prediction of the relative ability of a substance to induce sensitization.

Occlusive Irritant Dermatitis: When Is “Allergic” Contact Dermatitis Not Allergic?

CASE 1: A 38-year-old teacher presented with a 3- to 4-week history of a linear, erythematous, vesicular, and pruritic eruption of her left wrist. She had been wearing a new elastic bracelet for 4 weeks before the onset of her eruption. Although there was no history of allergy to rubber products or jewelry, an allergic contact dermatitis to rubber was suspected. Patch testing to rubber chemicals and the elastic bracelet revealed no reactions at 48, 72, and 96 hours. She stopped wearing the bracelet and used a corticosteroid cream with rapid resolution of the problem. The patient resumed wearing the bracelet, and there has been no recurrence in the past 2 months. CASE 2: A 12-year-old boy presented with a 1-month history of an itchy, scaly, erythematous 1-cm patch over the midline of his lower lip. The patient complained of tiny blisters initially with persistent erythema, mild scaling, and associated pruritus. The patient plays the saxophone and he had been practicing more intensely (3 to 4 h/d) for a musical competition. Allergic reaction to his wood reed was suspected, but patch testing with a moistened portion of his reed and reed shavings in a drop of water revealed no reaction at 48 and 72 hours. Treatment with hydrocortisone 1% cream bid for 3 days led to complete resolution of the dermitis and pruritus. Playing the saxophone 1 h/d has not led to any recurrence. CASE 3: A 33-year-old woman presented with erythema, scaling, and pruritus of 1 month's duration beneath her engagement and wedding rings, which were worn together on her left fourth finger (Figure 3). Although she had no history of previous sensitivity to earrings, watch clasp, blue jean rivets, or other jewelry, allergic contact dermatitis to nickel was suspected. Patch testing was performed to the common metal allergens nickel, cobalt, chromium, and gold. Readings at 48 hours and 1 week revealed no positive reactions. The patient wore her rings on the right hand for 1 week and used fluocinonide 0.5% cream twice daily for 1 week with resolution of the dermatitis. She has subsequently begun wearing the rings again on her left hand with care to dry her hands and rings after washing, and there has been no recurrence of her dermatitis.

The impact of various patient factors on contact allergy to nickel, cobalt, and chromate

Positive patch-test results to nickel, cobalt, and chromate alone and in combinations with one another are well known to occur. Patient factors that may play a role in isolated and concurrent sensitization to these allergens have not been studied in the US population. We sought to determine the prevalence of isolated and concurrent nickel, cobalt, and chromate sensitizations and to investigate the impact of various patient factors on their development. A retrospective analysis was carried out on patch-test data of 1187 patients evaluated at one US center from January 1, 1995, to December 31, 2004, 208 of whom had a positive reaction to at least one metal. Statistical analyses to evaluate associations of metal contact allergy with patient factors were performed using the chi(2) test and conditional odds ratio. All patients who reacted to metal had increased odds of cosensitization to another metal. Patients who reacted to nickel were more likely to be female. Those who reacted to chromate were more likely to be male and to have an occupational cause for their dermatitis. There was a strong trend for patients who reacted to cobalt to be non-Caucasian. All those who reacted to metal had increased odds of a history of atopic eczema. Chromate reactions and isolated cobalt reactions were less likely to have known relevance than other (nonmetal) allergens. Several metal allergy combinations showed a predilection toward specific dermatitis sites, especially the scalp, eyelids, ears, and lips. The study was a retrospective analysis, exploratory in nature, and had relatively small numbers of patients with particular multiple metal allergy combinations. This research confirms the sex predilections toward nickel and chromate allergy and suggests enhanced sensitivity to metals among those with atopic eczema. The results also serve to raise questions regarding occupationally related chromate allergy in men, the relevance of cobalt allergy, exposure patterns resulting in enhanced sensitivity to cobalt in non-Caucasians, and associations between metal allergens and dermatitis site. The answers to these questions require more detailed studies.

A multifactorial analysis of concurrent patch‐test reactions to nickel, cobalt, and chromate

Previous research indicates that positive patch tests to nickel (II) sulphate, cobalt (II) chloride and potassium dichromate commonly occur together. To further examine the relationship between nickel, cobalt, chromate, and the factors that may potentially be related to concurrent sensitizations to two or all three metal allergens, data from the Information Network of Dermatology Departments have been investigated. Women had a higher conditional odds of concurrent nickel-cobalt (OR = 6.80; 95% CI: 5.65-8.19) and nickel-chromate (OR = 2.13; 95% CI: 1.67-2.72) reactions than men. Construction workers had a significantly higher odds of cobalt-chromate reactions (OR = 13.89; 95% CI: 10.36-18.64), while the odds of isolated cobalt allergy was only 0.92 (95% CI: 0.48-1.74). Patients with underlying atopic eczema/dermatitis syndrome had a 40-90% higher chance of any positive outcome, which involved chromate. Polysensitization, defined as the number of positive reactions to standard series substances other than nickel, cobalt, and chromate, was also significantly associated with the concurrent reactions; moreover, steady and significant effect gradients were noted. This research confirms the occupational nature of cobalt-chromate concurrent reactions, in particular, in construction workers. Polysensitization, which is considered to represent susceptibility to delayed-hypersensitivity in general, is also associated with the concurrent reactions to the metals. Hence, not only coupled exposure, but also individual susceptibility may be responsible for concurrent reactions to metals in man.

Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line

It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-α, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1β. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a dose-dependent manner while non-sensitizers, such as SLS and methyl salicylate (MS), did not. To note, the metal allergens such as (NH 4) 2[PtCl 4], NiSO 4 and CoSO 4 augmented significantly only CD54 expression. Taking advantage of a cultured cell line, measurement of the co-stimulatory molecules, CD54 and CD86, on naive THP-1 cells following chemical exposure shows promise for the development of a simple, short-term in vitro sensitization test.