E V Warbrick

Syngenta, Bâle, Basel-City, Switzerland

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Publications (22)45.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Methylene chloride (dichloromethane) is used in a variety of industrial applications. To date, there has been no formal assessment of immunotoxicity attributed to methylene chloride. Studies were undertaken to examine whether methylene chloride has any potential to influence the integrity of immune function. For this purpose, Sprague-Dawley rats of both genders were exposed by inhalation to a single high dose (5000 ppm) of methylene chloride for 6 h/d, 5 d/wk for 28 d. This was considered the relevant route of administration, as not only is inhalation a primary route for human exposure to methylene chloride, but, also, the chemical is absorbed rapidly via the lungs. Under these conditions of exposure, methylene chloride failed to influence absolute or relative thymus weights in either gender and produced a significant reduction in relative, but not absolute, spleen weight in female rats only. Immunocompetence was measured as a function of the ability of treated animals to mount immunoglobulin M (IgM) antibody responses to sheep red blood cells (SRBC) as determined by enzyme-linked immunosorbent assay (ELISA). Exposure to methylene chloride did not affect antibody production. Evidence indicates that under these conditions of exposure, methylene chloride did not compromise immune function.
    Journal of Toxicology and Environmental Health Part A 08/2003; 66(13):1207-19. · 1.73 Impact Factor
  • R J Dearman, E V Warbrick, R Skinner, I Kimber
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    ABSTRACT: The cellular and molecular mechanisms that result in the induction of chemical respiratory sensitization are unclear, although there is evidence for the development of T helper (Th) 2 type responses and, in some cases, the production of IgE. We have compared cytokine secretion patterns stimulated by topical exposure of BALB/c strain mice or Brown Norway (BN) strain rats to the reference respiratory allergen trimellitic anhydride (TMA), or to the reference contact allergen 2,4-dinitrochlorobenzene (DNCB). Under conditions where TMA and DNCB provoke similar levels of immune activation [increases in lymph node cell (LNC) cellularity and proliferation] divergent cytokine expression patterns are elicited. TMA-activated LNC isolated from BALB/c mice or BN rats elaborated high levels of the Th2-type cytokines interleukin (IL)-10 and IL-13, but relatively little of the Th1-type cytokines IL-12 or interferon gamma. For LNC derived from both species there was a requirement for restimulation in vitro with the mitogen concanavalin A for IL-4 production. Generally, DNCB-stimulated LNC displayed the converse type 1 cytokine phenotype. The cytokine secretion profiles of LNC isolated from BN rats were considerably more variable than those observed for LNC from BALB/c mice. Statistically significant differences (P<0.01) between DNCB- and TMA-activated LNC were recorded for all cytokines in BALB/c strain mice. For the BN rat, differences reached statistical significance (P<0.01) only for the expression of IL-4 and IL-13. These data demonstrate that the intrinsic ability of DNCB and TMA to promote preferential Th1- and Th2-type responses, respectively, is species-independent and provide further evidence that chemical respiratory allergens are associated with polarized Th2-type responses. For the prospective assessment of chemical respiratory allergens as a function of induced cytokine secretion profiles, however, these data suggest that the use of the BALB/c strain mouse will provide the more robust method.
    Food and Chemical Toxicology 01/2003; 40(12):1881-92. · 3.01 Impact Factor
  • E Vicky Warbrick, Rebecca J Dearman, Ian Kimber
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    ABSTRACT: A variety of chemicals can cause sensitisation of the respiratory tract and occupational asthma, including certain acid anhydrides, diisocyanates and reactive dyes. As yet, no well-validated methods are available for the toxicological evaluation of the respiratory sensitising potential of chemicals. One approach which has been explored recently is the evaluation of induced IgE responses or cytokine expression patterns in rats or mice following topical exposure to chemical. Thus, it has been demonstrated that topical exposure of rodents to respiratory sensitising chemicals, but not to contact allergens, causes a dose-dependent and time-related increase in the concentration of total IgE. Using the reference respiratory allergen trimellitic anhydride (TMA), we have considered here the influence of route of exposure on the nature of induced immune responses. Specific IgG and IgE antibody responses and changes in total serum concentration of IgE have been measured following exposure of Brown Norway (BN) starin rats to TMA by topical administration or by inhalation. Exposure to TMA by both routes resulted in the stimulation of specific IgG and IgE antibody, although responses were considerably more vigorous after dermal exposure. Topical treatment also provoked marked and sustained increases in total serum IgE levels, whereas exposure via the respiratory tract stimulated a more transient elevation of this immunoglobulin in a minority of animals which reached statistical significance only at the highest dose group. The lesser vigour of the immune response following inhalation exposure is likely to be related to the considerably lower total antigenic dose which is delivered by this route. Nevertheless, these results show that the nature of immune response with respect to antibody isotype profile provoked by topical administration of TMA is qualitatively comparable with that stimulated by inhalation exposure to the same chemical. For the purposes of hazard assessment and identification of potential chemical respiratory allergens as a function of induced changes in serum IgE concentration, however, the evidence is that topical administration of test material is the preferred route of exposure.
    Toxicology 05/2002; 172(3):157-68. · 4.02 Impact Factor
  • E V Warbrick, R J Dearman, I Kimber
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    ABSTRACT: A variety of chemicals can cause sensitization of the respiratory tract and occupational asthma that may be associated with IgE antibody production. Topical exposure to chemical respiratory allergens such as trimellitic anhydride (TMA) has been shown previously to induce increases in the total serum concentration of IgE in BALB/c strain mice. Contact allergens such as 2,4-dinitrochlorobenzene (DNCB), which apparently lack respiratory sensitizing potential, fail to provoke similar changes. However, it became apparent with time that there was some inter-animal variation in constitutive and inducible IgE levels. We have now examined the influence of topical exposure to TMA and DNCB on serum IgE levels in the Brown Norway (BN) rat. Such animals can be bled serially and thus it is possible to perform longitudinal analyses of changes in serum IgE concentration. The kinetics of IgE responses therefore can be followed on an individual animal basis, allowing discrimination between transient and sustained increases in serum IgE concentration. Rats (n = 5) were exposed on shaved flanks to 50% TMA, to 1% DNCB (concentrations that elicit comparable immune activation with respect to draining lymph node cellularity and proliferation) or to vehicle alone. Total IgE was measured by enzyme-linked immunosorbent assay in serum samples taken prior to and 14-42 days following initial exposure. Those animals having high pre-existing IgE levels (>1.0 microg ml(-1)) were excluded from subsequent analyses. The levels of serum IgE in the majority of rats exposed to DNCB or vehicle alone remained relatively stable throughout the duration of all the experiments conducted, although some animals displayed transient increases in serum IgE. Only TMA treatment was associated with a significant and sustained increase in the level of serum IgE in the majority of experiments. The elevated concentrations of IgE induced by topical exposure to TMA are persistent, the results reported here demonstrating that induced changes in IgE are maximal or near maximal at approximately 35 days, with a significant increase in IgE demonstrable for at least 42 days following the initiation of exposure. Interestingly, although TMA and DNCB at the test concentrations used were found to be of comparable overall immunogenicity with regard to lymph node activation and the induction of lymph node cell proliferation, there were apparent differences in humoral immune responses. Thus, not only did exposure to TMA stimulate increases in total serum IgE concentration and the production of specific IgE antibody, but also a more vigorous IgG antibody response was provoked by TMA compared with DNCB. These data suggest that the measurement of induced changes in serum IgE concentration in the BN strain of rat is able to differentiate between different classes of chemical allergen. Given the inter-animal variation in IgE production, it would be prudent to incorporate a concurrent assessment of responses induced by treatment with TMA as a positive control against which to assess the activity of other test materials.
    Journal of Applied Toxicology 01/2002; 22(1):1-11. · 2.60 Impact Factor
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    ABSTRACT: The murine local lymph node assay (LLNA) assesses skin sensitization potential as a function of proliferative responses induced in lymph nodes draining the site of topical exposure to test chemical. It has been shown that interpolation of LLNA dose-response data to define the concentration of test chemical required to induce a 3-fold stimulation of proliferation (EC3) offers the prospect of a quantitative index of the relative potency of a contact allergen. Initial studies have demonstrated that there exists a strong (inverse) correlation between EC3 values and contact allergenic potency in humans. Thus, materials with a low EC3 value were more potent contact allergens in humans. However, it is necessary to examine a wide range of allergens to demonstrate that such correlations are generally true. Thus, in the present study, 10 aldehydes of varying degrees of allergenicity in man were evaluated in the LLNA and their EC3 values derived. Formaldehyde was regarded as the strongest allergen in man and also had the lowest EC3 value, 0.35% (equivalent to 0.93% formalin). In contrast, the extremely weak allergen vanillin and the non-sensitizer ethyl vanillin both had EC3 values of >50%. For the remaining 7 aldehydes, there was a close similarity between what is judged to be their rank order of allergenicity in humans and EC3 values derived from analysis of LLNA data. These results support further the utility of EC3 determinations in the LLNA as a measure of the relative potency of a contact allergen.
    Contact Dermatitis 08/2001; 45(2):89-94. · 2.93 Impact Factor
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    ABSTRACT: It has been demonstrated previously that there exists an incomplete correlation between the skin sensitizing potential of chemicals and their mutagenic properties as judged by activity in the Salmonella mutation assay. More recently, it has been proposed that there may exist a broader association between carcinogenicity in rodents (including non-genotoxic carcinogenesis) and skin sensitizing activity. To explore further these putative relationships we have here examined the skin sensitizing potential of two non-genotoxic rodent carcinogens which are generally considered not to represent a carcinogenic hazard in humans (limonene and saccharin) and of three genotoxic rodent carcinogens (vinylidene dichloride, ethyl acrylate and bisphenol A diglycidyl ether). For this purpose we have used the local lymph node assay (LLNA), a method for the identification and characterization of skin sensitizing chemicals that has recently been recognized as a stand-alone method for hazard identification purposes. Activity in the LLNA was compared with the results of Salmonella tests conducted previously. This small series of investigations reveals that there exists no general relationship between skin sensitizing potential and rodent carcinogenicity. Furthermore, although a general correlation does exist between mutagenic activity and skin sensitization, this association is not universal and activity in the Salmonella mutation assay does not necessarily imply skin sensitizing potential. Collectively these data suggest that it is inappropriate currently to recommend the use of skin sensitization tests as an adjunct to conventional approaches to the evaluation of potential carcinogenicity.
    Toxicology 06/2001; 163(1):63-9. · 4.02 Impact Factor
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    ABSTRACT: The murine local lymph node assay (LLNA) can be used to determine the relative skin sensitizing potency of chemicals via interpolation of the quantitative dose response data generated. Using this approach we have demonstrated previously that the vehicle matrix in which a chemical allergen is encountered on the skin can have a significant influence on sensitizing potency. Estimates of relative potency are calculated from LLNA dose responses as a function of the mathematically derived EC3 value, this being the concentration estimated to induce a stimulation index (SI) of 3. To investigate further the influence of application vehicle on sensitizing potency, the LLNA has been used to examine the activity of four recognized human contact allergens: isoeugenol and cinnamic aldehyde, two fragrance chemicals; 3-dimethylaminopropylamine (a sensitizing impurity of cocamidopropyl betaine, a surfactant used in shower gel) and dibromodicyanobutane (the sensitizing component of Euxyl K 400, a preservative used in cosmetics). The four chemicals were applied in each of seven different vehicles (acetone: olive oil [4 : 1]; dimethylsulphoxide; methylethylketone; dimethyl formamide; propylene glycol; and both 50 : 50 and 90 : 10 mixtures of ethanol and water). It was found that the vehicle in which a chemical is presented to the epidermis can have a marked effect on sensitizing activity. EC3 values ranged from 0.9 to 4.9% for isoeugenol, from 0.5 to 1.7% for cinnamic aldehyde, from 1.7 to > 10% for dimethylaminopropylamine and from 0.4 to 6.4% for dibromodicyanobutane. These data confirm that the vehicle in which a chemical is encountered on the skin has an important influence on the relative skin sensitizing potency of chemicals and may have a significant impact on the acquisition of allergic contact dermatitis. The data also demonstrate the utility of the LLNA as a method for the prediction of these effects and thus for the development of more accurate risk assessments.
    International journal of cosmetic science 04/2001; 23(2):75-83.
  • E V Warbrick, R J Dearman, I Kimber
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    ABSTRACT: The mouse local lymph node assay (LLNA) is currently used for the prospective identification of chemicals that have the potential to cause skin sensitization and allergic contact dermatitis. In this respect, the assay has been fully and formally evaluated and validated, and has been accepted recently as a stand-alone method for the identification of potential skin sensitizers. The assay involves topical application of test substance and the subsequent measurement of proliferative responses in the lymph nodes draining the site of exposure. The testing of new drug entities using a similar assay technique could offer a potential alternative for the identification of potential drug allergens. Currently, the popliteal lymph node assay (PLNA), or modifications of it, are used in research studies for the identification of drugs which have the potential to cause allergic or autoimmunogenic reactions. The PLNA involves subcutaneous application of test substance into the hind footpad, followed by the measurement of proliferative responses, or other parameters of immune activation, in the popliteal lymph nodes. However, these assays have not been validated systematically and the potential utility of a modified LLNA for use in the identification of such compounds is discussed.
    Current opinion in drug discovery & development 02/2001; 4(1):60-5. · 5.12 Impact Factor
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    ABSTRACT: The murine local lymph node assay (LLNA) is a predictive test for the identification of chemicals that have the potential to cause skin sensitization. Since its original development, the assay has been the subject of national and international evaluation studies and extensive comparisons with guinea pig tests and human data. On the basis of these investigations, the LLNA has recently been endorsed by ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) as a stand-alone method for skin sensitization hazard identification. At the same time, ICCVAM confirmed that, although the LLNA is not an in vitro method, it does represent a refinement in the way animals are used and can provide a means for reducing the number of animals used in sensitization hazard assessment. The investigations described here were designed to explore further the ability of the LLNA to identify accurately those chemicals that cause allergic contact dermatitis in humans. To that end we have measured, amongst 3 independent laboratories, LLNA responses induced by a total of 18 test chemicals, 11 of which are known to cause skin sensitization and 7 of which are believed not to be associated with any significant evidence of allergic contact dermatitis in humans. The LLNA correctly classified 16 of the 18 materials. The 11 chemicals tested which are associated with allergic contact dermatitis in humans were found to be positive in the LLNA. Of the 7 materials believed to be non-sensitizers, 5 were negative in the LLNA and 2 produced positive results. Collectively, these data provide additional evidence that the LLNA is able to discriminate skin sensitizers from those chemicals which do not possess a significant skin sensitization potential and thus provides a method for hazard identification that offers important animal welfare benefits.
    Contact Dermatitis 09/2000; 43(2):95-102. · 2.93 Impact Factor
  • Contact Dermatitis 04/2000; 42(3):164-5. · 2.93 Impact Factor
  • E. V. Warbrick, R. J. Dearman, I. Kimber
    Toxicology. 01/2000; 148(1):40-41.
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    ABSTRACT: The murine local lymph node assay (LLNA) has been validated as an alternative method for the identification of skin sensitization hazards. Contact allergens are identified as a function of proliferative responses induced in draining lymph nodes. The quantitative nature of the LLNA data also provides the opportunity of assessing relative potency by reference to dose response analyses. In the current investigations, the influence of vehicle on the skin sensitization potency of a known skin sensitizer (1,4-dihydroquinone) was assessed. 1, 4-dihydroquinone was tested in the LLNA using 7 different vehicle systems in each of 2 independent laboratories. Results from the 2 laboratories were almost identical. LLNA dose response data were interpolated to derive the estimated concentration (EC) of 1, 4-dihydroquinone necessary to cause a three-fold stimulation of proliferation compared with controls, the EC3 value. The vehicles used and mean EC3 values obtained were: methyl ethyl ketone 0.07%, acetone 0.08%, acetone/olive oil (80/20 v/v) 0.15%, dimethyl formamide 0.22%, dimethyl sulfoxide 0.4%, and propylene glycol and acetone/saline (50/50 v/v) vehicles gave negative results. However, when tested at higher concentrations, positive results were obtained in these vehicles. These data reveal that the vehicle in which a chemical is encountered in the skin can have a significant impact on a quantitative measure of skin sensitization potency. The implication is that accurate assessment of risk to humans will require an understanding of the matrix in which skin exposure is likely to occur.
    American Journal of Contact Dermatitis 01/2000; 10(4):213-8.
  • E. V. Warbrick, R. J. Dearman, I. Kimber
    Toxicology. 01/2000; 148(1):45-45.
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    ABSTRACT: Occupational exposure to certain acid anhydrides, including trimellitic anhydride (TMA), maleic anhydride (MA), phthalic anhydride (PA), hexahydrophthalic anhydride (HHPA) and methyltetrahydrophthalic anhydride (MTHPA), has been associated with the development of respiratory allergy or asthma. There is considerable debate about the mechanisms through which such chemicals may cause respiratory sensitization, particularly concerning a universal requirement for specific IgE antibody. Despite the controversy regarding an obligatory role for IgE, there is a growing consensus that chemical respiratory hypersensitivity is associated with the selective development of T lymphocytes with a type 2 (Th2) phenotype. In the current investigations we have characterized in mice the nature of immune responses provoked by prolonged topical exposure to five acid anhydrides. Under application conditions where similar overall immunogenicity was achieved, we have compared cytokine responses induced by PA, MA, HHPA and MTHPA with those provoked by concurrent exposure to TMA or to the reference contact allergen 2, 4-dinitrochlorobenzene (DNCB). Lymph node cells (LNC) draining the site of topical exposure to DNCB invariably expressed high levels of the type 1 cytokines interferon-gamma (IFN-gamma) and interleukin-12 (IL-12), but only low levels of the type 2 cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10). In each experiment, TMA-activated LNC displayed the converse, type 2, phenotype of cytokine production. The other acid anhydrides in each case provoked a type 2 cytokine secretion profile, with comparable IL-10 expression but somewhat less vigorous IL-4 production compared with that observed following exposure to the reference respiratory allergen TMA. In every experiment relatively low levels of IFN-gamma and IL-12 were elaborated by acid anhydride-activated LNC, with the exception of PA-stimulated LNC that displayed increased amounts of IL-12 in comparison with other acid anhydrides. Thus, prolonged topical exposure of mice to five different acid anhydrides in each case resulted in the development of a predominantly Th2-type cytokine secretion phenotype, consistent with the ability of these materials to provoke asthma and respiratory allergy through a type 2 (possibly IgE-mediated) mechanism. Taken together with the results of previous investigations with a wider range of chemical allergens, these data suggest that induced cytokine secretion patterns or 'fingerprints' allow discrimination between contact and respiratory allergens and consequently represent a suitable approach to prospective evaluation of respiratory sensitization hazard.
    Journal of Applied Toxicology 01/2000; 20(3):221-30. · 2.60 Impact Factor
  • Toxicology. 01/2000; 148(1):46-47.
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    ABSTRACT: The murine local lymph node assay (LLNA) is a method for the identification of skin sensitizing chemicals in which activity is measured as a function of proliferative responses induced in draining lymph nodes following topical exposure of mice to the test material. More recently, the LLNA has also been used for the determination of relative skin sensitizing potency based upon the mathematical derivation of an EC3 value, this being the estimated concentration of test chemical necessary to provoke a 3-fold increase in lymph-node cell-proliferative activity compared with concurrent vehicle-treated controls. Here we describe the use of the LLNA to determine the influence of vehicle on the skin-sensitizing potency of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), the active ingredient of preservatives such as Kathon CG. To this end, LLNA responses to MCI/ MI were measured using the vehicles 4:1 acetone:olive oil (AOO), methyl ethyl ketone, dimethylsulfoxide, dimethylformamide, propylene glycol (PG) and acetone. It was found that the vehicle in which MCI/MI was applied had a substantial impact on activity, with derived EC3 values varying from 0.0049% with AOO to 0.048% with PG. With the other vehicles, EC3 values ranged from 0.0068 to 0.0076%. The skin sensitizing potency of MCI/MI as judged from LLNA responses is consistent with what is known of the requirements for sensitization in humans. It is proposed that the LLNA not only provides a method for determination of relative skin sensitizing potency, but is also appropriate for assessing the influence of vehicle matrix on sensitizing activity.
    Contact Dermatitis 12/1999; 41(6):325-9. · 2.93 Impact Factor
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    ABSTRACT: Interleukin (IL) 12 is a heterodimeric cytokine which stimulates IFN-gamma production and promotes the development of type 1 T helper cells and T cytotoxic cells from their respective precursors. We have described previously that contact allergens such as 2,4-dinitrochlorobenzene (DNCB), and respiratory allergens such as trimellitic anhydride (TMA) induce discrete type 1 and type 2 cytokine secretion patterns, respectively, following repeated topical exposure of BALB/c strain mice. Under such conditions, we have now examined production by draining LNC of the inducible subunit of IL-12 (p40) and p40 and p35 subunit mRNA expression. Cultured LNC prepared from mice treated with DNCB secreted significantly more IL-12 p40 protein than did TMA- or vehicle-activated LNC, such differences becoming more pronounced as the duration of culture increased. Maximal levels of mRNA expression of the IL-12 p40 subunit were observed after 6-24 h of culture in all treatment groups and declined thereafter. Somewhat higher levels were induced following exposure to DNCB, these differences only reached statistical significance at 24 h of culture. Expression of this subunit by LNC from all treatment groups declined with time in culture. Levels of IL-12 p35 mRNA expression were comparable in cultured LNC prepared from allergen and vehicle treated mice and remained constant throughout the entire culture period. These data indicate that the divergent T cell cytokine responses seen in response to contact and respiratory allergens are associated with differential production of IL-12 p40 protein in the absence of substantial changes in the expression of mRNA for either subunit.
    Toxicology 02/1999; 132(1):57-66. · 4.02 Impact Factor
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    ABSTRACT: The murine local lymph node assay (LLNA) is a method for the prospective identification of skin sensitizing chemicals. Proliferative responses induced in lymph nodes draining the site of topical application of the test chemical are measured and those chemicals that induce a stimulation index of three or more compared with concurrent vehicle-treated controls are considered to have the potential to cause skin sensitization. Dose-response data from the LLNA may be used to derive an estimate of relative skin sensitizing potency, based upon derivation of the concentration of chemical required to cause a stimulation index of 3 (EC3 value) as calculated by linear interpolation. The purpose of the present investigations was to examine the stability of LLNA responses and the consistency of derived EC3 values induced by the contact allergen paraphenylenediamine (PPD). Analyses were conducted once a month over a 4-month period in each of two independent laboratories. In all assays, and in both laboratories, PPD elicited a positive response. Although some minor differences in responses between and within laboratories were observed, the derived EC3 values were generally very consistent. In Laboratory 1, EC3 values varied between 0.06 and 0.09% PPD, whereas in Laboratory 2 the range was 0.09-0.20%. These EC3 values are consistent with clinical experience of this material insofar as it is a common and relatively potent cause of allergic contact dermatitis in humans. Taken together, these data confirm the stability of LLNA responses both with time and between laboratories and provide additional support for the use of derived EC3 values in the assessment of relative skin sensitizing potency.
    Journal of Applied Toxicology 01/1999; 19(4):255-60. · 2.60 Impact Factor
  • I Kimber, E V Warbrick, R J Dearman
    Human &amp Experimental Toxicology 11/1998; 17(10):537-40. · 1.45 Impact Factor
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    ABSTRACT: It has been shown previously that cytokine secretion patterns characteristic of the activation of discrete responses by functional subsets of T cells of type 1 and type 2, respectively, are elicited following topical exposure of BALB/c strain mice to chemical contact and respiratory allergens. In order to investigate if the differences in protein profiles are paralleled by changes in steady-state mRNA levels we have now investigated cultured draining lymph node cell (LNC) cytokine mRNA expression profiles by reverse transcriptase-polymerase chain reaction (RT-PCR) under conditions where divergent cytokine secretion is observed. Mice were exposed topically by repeated application of the respiratory allergen trimellitic anhydride (TMA) or of the contact allergen 2,4-dinitrochlorobenzene (DNCB). An elevation in the expression of mRNA for interleukin 4 (IL-4) and interleukin 10 (IL-10) by LNC from both TMA- and DNCB-treated animals was observed within 6 h of culture, reaching maximal levels after 72 h. Relative mRNA levels for both of these type 2 cytokines were considerably higher in cultured cells derived from TMA-exposed mice, compared with those from DNCB-treated animals. Transient low levels of the type 1 cytokine interferon y (IFN-gamma) were observed in response to treatment with TMA, whereas a substantial upregulation of IFN-gamma gene expression was seen from 24 h onwards in cultured LNC derived from DNCB-exposed mice. Changes in cytokine mRNA in allergen-activated LNC preceded protein production, although the kinetic profiles were similar. These data suggest that the divergent cytokine secretion profiles exhibited by mice treated by repeated topical exposure to contact and respiratory allergens are controlled primarily at the level of transcription. The RT-PCR methodology described herein may be more sensitive for the detection of cytokines expressed in low copy number, such as IL-4, where previously it has been found necessary to stimulate LNC with mitogen to elicit measurable levels of protein secretion. However, this technique was not found to offer major practical advantages when compared with protein detection methods (enzyme-linked immunosorbent assays) for the routine predictive characterization of chemicals as a function of cytokine 'fingerprinting'.
    Journal of Applied Toxicology 01/1998; 18(3):205-13. · 2.60 Impact Factor