Mouse Model Of Contact Hypersensitivity Research Articles

Investigation of unmatured hematopoietic cell migration in a mouse model

Abstract The objective of this work was to examine the migration of transplanted bone marrow hematopoietic lin− cell population using the BALB/c mouse contact hypersensitivity model in vivo and to determine the time point at which they reach the site of injury (paw edema) as well as other undamaged organs, such as liver and spleen. Female BALB/c mice with induced contact hypersensitivity reaction were intravenously injected with 1×106 cells/mouse lin− cells, labeled with PKH67. The presence of lin− stained cells in mouse tissue sections was evaluated by fluorescent microscopy. After one hour, the labeled cells were found in mice paw edema and liver, and after 4 hours in spleen tissue. Migrated hematopoietic lin− cells remained in liver tissue for 48 h, and in spleen and paw edema at least for 72 h. Migrated stained cells in untreated paw were not found. The results prove that bone marrow unmatured hematopoietic cells are first found in paw edema, where they participate in the inhibition of tissue inflammation; these cells subsequently migrate to the liver and are found in the spleen shortly afterwards.

Prostaglandin I2–IP Signaling Promotes Th1 Differentiation in a Mouse Model of Contact Hypersensitivity

PGI(2), which exerts its actions via its specific Gs-coupled I prostanoid receptor (IP), is known to be present in the lymph nodes, but its roles in acquired cutaneous immune responses remain unclear. To investigate the role of PGI(2)-IP signaling in cutaneous immune responses, we applied IP-deficient (Ptgir(-/-)) mice to contact hypersensitivity as a model of acquired immune response and found that Ptgir(-/-) mice exhibited a significantly decreased contact hypersensitivity response. Lymph node cells from sensitized Ptgir(-/-) mice exhibited decreased IFN-gamma production and a smaller T-bet(+) subset compared with control mice. PGI synthase and IP expression were detected in dendritic cells and T cells, respectively, by quantitative real-time PCR analysis, suggesting that PGI(2) produced by dendritic cells acts on IP in T cells. In fact, in vitro Th1 differentiation was enhanced by an IP agonist, and this enhancement was nullified by protein kinase A inhibitor. These results suggest that PGI(2)-IP signaling promotes Th1 differentiation through a cAMP-protein kinase A pathway and thereby initiates acquired cutaneous immune responses.

Phthalate esters reveal skin-sensitizing activity of phenethyl isothiocyanate in mice

Phenethyl isothiocyanate (PEITC) is a constituent of edible cruciferous vegetables and has received attention due to its potential cancer chemopreventive activity. Although its protein-binding activity is known, PEITC has not been studied as a contact sensitizer. We previously demonstrated that phthalate esters, including dibutyl phthalate (DBP) and di-n-propyl phthalate (DPP), enhance skin sensitization in a fluorescein isothiocyanate (FITC)-induced contact hypersensitivity mouse model. In this study, we examined whether DBP and DPP enhance skin sensitization to haptens other than FITC. During this study, we tested PEITC as a contact sensitizer. BALB/c mice were epicutaneously sensitized with a suboptimal dose of a hapten with or without a phthalate ester. Sensitization was evaluated as the ear swelling response after a challenge with the respective hapten. DBP and DPP did not enhance the sensitization to two T-helper 1-type (2,4-dinitrofluorobenzene and oxazolone) or three T-helper 2-type (trimellitic anhydride, methylenediphenyl 4,4′-diisocyanate, and tolulene 2,4-diisocyanate) haptens. In contrast, DBP and DPP enhanced the sensitization to two FITC analogues (eosin 5-isothiocyanate and rhodamine B isothiocyanate) as well as to PEITC. Adjuvant effects of DBP and DPP were observed in contact hypersensitivity to haptens other than FITC, including a food ingredient PEITC.

A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses (97.1)

Abstract B cells mediate multiple functions that influence immune and inflammatory responses. While B cells contribute to disease in most autoimmune mouse models, we have also found that B cells have regulatory functions and inhibit inflammation. Specifically, T cell-mediated inflammation in a mouse model of contact hypersensitivity was exaggerated in CD19-deficient (CD19-/-) mice and wild type mice depleted of CD20+ B cells, while inflammation was substantially reduced in mice with hyperactive B cells due to CD19 overexpression (hCD19Tg). These inflammatory responses were negatively regulated by a unique CD1dhiCD5+ B cell subset that was absent in CD19-/- mice, represented only 1-2% of spleen B220+ cells in wild type mice, but was expanded to ~10% of spleen B220+ cells in hCD19Tg mice. Adoptive transfer of these CD1dhiCD5+ B cells normalized inflammation in wild type mice depleted of CD20+ B cells and in CD19-/- mice. Remarkably, IL-10 production was restricted to this CD1dhiCD5+ B cell subset, with IL-10 production diminished in CD19-/- mice, yet increased in hCD19Tg mice. Thereby, CD1dhiCD5+ B cells represent a unique subset of potent regulatory B cells that we have labeled as "B10 cells" due to their unique production of IL-10 and the fact that other regulatory B cell subsets are likely to exist.

TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity

We have revealed that local stimulation of sensory neurons is involved in the adjuvant effect of dibutyl phthalate (DBP) in a fluorescein isothiocyanate-induced mouse contact hypersensitivity model. Transient receptor potential (TRP) A1 and TRPV1 seemed to be candidate DBP targets. Here we directly demonstrated that DBP activates a subset of neurons in mouse dorsal root ganglia responsive to TRPA1 and TRPV1 agonists. TRPA1 and TRPV1 activation was further demonstrated using cultured cells expressing TRP channels. Among structurally different phthalate esters, there is a positive relationship between the activation of TRPA1- or TRPV1-expressing cells and the adjuvant effect.

Anti‐inflammatory and immune‐regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.

Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.

From innate to adaptive immune responses in contact hypersensitivity

To summarize recent findings that highlight the importance of the innate inflammatory immune responses in contact dermatitis and their role for the adaptive T-cell response to contact allergens. Implications for anti-inflammatory therapy based on recent reports are discussed. Allergic contact dermatitis is studied widely in the mouse model. Recent work has identified an important role of innate pattern recognition receptors and innate immune cells in contact hypersensitivity. The role of skin dendritic cells has been studied with novel approaches for in-vivo depletion. New findings were made in the field of anti-inflammatory therapy either by uncovering new aspects of pathomechanisms or by the use of drugs that target different elements of the inflammatory cascade. Inflammation is a pivotal element of allergic contact dermatitis. Studies in the mouse contact hypersensitivity model are beginning to shed light on the still largely unknown molecular mechanisms that enable contact allergens such as chemicals, metal ions and plant compounds to initiate the inflammatory innate immune response. This is a prerequisite for the adaptive immune response to occur. The recent progress in research points out the great potential of anti-inflammatory therapy covering a wide range of molecular targets.

Expression of Chemokine Receptor CCR4 and Its Ligands (CCL17 and CCL22) in Murine Contact Hypersensitivity

Chemokine receptor CCR4 and its ligands (CCL17 and CCL22) are important for the recruitment of memory T cells into the skin in various cutaneous immune diseases. However, information on CCR4 and its ligands in contact hypersensitivity is relatively limited. In this study, we investigated the expression of CCR4, CCL17, and CCL22 in a mouse model of contact hypersensitivity to oxazolone. Contact sensitization to oxazolone increased the proportions of memory CD4+ T cells in the draining lymph nodes, spleen, and peripheral blood. Although CCR4+ mRNA and CCR4+ cells were detectable in naive mouse lymph nodes, they significantly increased in the sensitized mice. The majority of CCR4+ cells in both control and sensitized mouse lymph nodes were CD4+ T cells. In the skin of naive mice, the mRNAs for CCR4, CCL17, and CCL22 were detectable, but only CCL17 and CCL22 proteins were constitutively expressed in the skin, particularly in the epidermis. Interestingly, the mRNAs for CCR4 and its two ligands were significantly elevated in the inflamed skin of mice with contact hypersensitivity to oxazolone. Furthermore, a subpopulation of cells that infiltrated the skin was CCR4+ cells. Finally, the expression of CCL17 and CCL22 proteins was significantly enhanced in the epidermis of inflamed skin. Thus, our study provides direct evidence for the presence of CCR4 and its ligands in mouse contact hypersensitivity.

Oligonucleotides Suppress IL-8 in Skin Keratinocytes In Vitro and Offer Anti-Inflammatory Properties In Vivo

DNA codes for genetic information. Furthermore, recent findings suggest that DNA offers additional function, particularly in the recognition of microorganisms. In this study, we investigated two classes of oligodeoxynucleotides (ODN) in skin keratinocytes; namely, an ODN comprising two cytidine-phosphate-guanosine (CpG) motifs (CpG-1-phosphorothioate (PTO)) and a poly-cytidine (Non-CpG-5-PTO) as control. Both fluorescence-tagged ODN were rapidly taken up by cells and accumulated already after 5 minutes in perinuclear compartments. In order to test whether ODN convey immunological effects in keratinocytes, secretion of IL-8 was measured. Interestingly, both CpG-1-PTO and Non-CpG-5-PTO suppressed basal and tumor necrosis factor alpha-induced IL-8 levels measured in cell culture supernatants. Experiments using deletion mutant revealed a critical length of approximately 16 nucleotides conveying IL-8 suppression. Studies regarding the ODN backbone offered that PTO bondings are critical for significant IL-8 suppression. In order to substantiate the anti-inflammatory response, a contact hypersensitivity mouse model was utilized. Topical application of Non-CpG-5-PTO-containing ointments reduced ear thickness in sensitized mice. Taken together, these findings suggest an anti-inflammatory effect of ODN in epithelial cells in vitro and in vivo, indicating that DNA molecules offer distinct biological activities restricted to the physiological compartment applied. This effect seems to be independent from Toll-like receptor 9.

Effects of Phthalate Esters on Dendritic Cell Subsets and Interleukin‐4 Production in Fluorescein Isothiocyanate‐Induced Contact Hypersensitivity

Phthalate esters with short alkyl chains, such as di-ethyl (DEP), di-n-propyl (DPP), and di-butyl phthalate (DBP), have adjuvant effects on an FITC-induced contact hypersensitivity mouse model. The adjuvant effects of DPP and DBP are associated with enhanced trafficking of FITC-presenting CD11b(+) dendritic cells (DC). DEP has relatively weak activity as to FITC-positive cell migration. Here we demonstrated that DBP and DPP also increased the number of FITC-positive CD8alpha(+) DC in draining lymph nodes. We also found enhanced production of interleukin-4 in draining lymph nodes after FITC sensitization with DEP, DPP, or DBP, suggesting an additional adjuvant mechanism of phthalate esters.

An anti-inflammatory effect of murine fetal liver cells in BALB/c mouse contact hypersensitivity model

Anti-inflammatory effects of murine fetal liver (FL) cells were studied using BALB/c mouse contact hypersensitivity (paw edema) model. Paw weight differences, lymphatic organ weights, hematological and histological indices as well as proinflammatory (TNF-α) and anti-inflammatory (IL-10) cytokine levels in sera were evaluated. Immunophenotyping revealed that both murine FL homogenate cells (HC) and FL hematopoietic stem cells (HSC) express CD117 and CD38 surface markers. Single doses of 1×106 cells/mouse and 2×106 cells/mouse of FL HC as well as of FL HSC, when used separately, all statistically significantly (p<0.05) inhibited paw edema, but the lower dose was more effective and giving results similar to that of prednisolone. Either dose of FL HC or FL HSC studied had no significant influence on lymphatic organ weights; no significant changes were also observed in blood indices. The data of cytokine studies showed that TNF-α concentration in sera of mice treated with either FL HC or FL HSC at a dose of 1×106 cells/mouse was statistically significantly (p<0.001) lower than that of the control mice. A concentration of IL-10 was statistically significantly higher (p<0.01) in mice treated with a dose of 1×106 cells/mouse of FL HC but not with the same dose of FL HSC as compared to the control group. Histological examination revealed better effects of a dose of 1×106 cells/mouse of FL HC when compared with the same dose of FL HSC as in regard to reduction of edema thickness and cell infiltration.

Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate

Many different types of phthalate ester are used as plasticizers and are thus found in the air. There have been several studies that suggest an association between allergies and phthalate esters. We previously found that di-butyl phthalate (DBP) has an adjuvant effect in a mouse contact hypersensitivity model, in which fluorescein isothiocyanate (FITC) is involved as an immunogenic hapten. We examined whether other phthalate esters enhance the process of sensitization to FITC by facilitating the trafficking of FITC-presenting dendritic cells or macrophages from skin sites to draining lymph nodes. Mice were epicutaneously sensitized with FITC dissolved in acetone containing a phthalate ester. Sensitization was evaluated as ear swelling after a challenge with FITC. Draining lymph node cells obtained 24 h after skin sensitization were examined for FITC fluorescence by means of flow cytometry. FITC-positive cells were characterized with anti-CD11c and anti-CD11b by three-colour flow cytometry. When mice were sensitized with FITC in acetone containing DBP or di-n-propyl phthalate (DPP), strong enhancement of the ear-swelling response was observed. Di-methyl phthalate (DMP) and di-ethyl phthalate (DEP) were less effective but produced some enhancement. Consistent enhancement was not observed with di-(2-ethylhexyl) phthalate or di-isononyl phthalate. Upon sensitization in the presence of DBP or DPP, the number of FITC-positive dendritic cells (total CD11c+ as well as CD11c+/CD11b+) was increased in draining lymph nodes. As to the other four phthalate esters, there was no significant increase in the FITC-positive cell number in the draining lymph nodes. During the process of sensitization to FITC, DBP, and DPP exert strong adjuvant effects that are associated with enhancement of trafficking of antigen-presenting dendritic cells from the skin to draining lymph nodes.

Detection of Vascular Expression of E-selectin in Vivo with MR Imaging

To develop a contrast agent for targeting E-selectin expressed on activated vascular endothelium and to evaluate detection of the agent with magnetic resonance (MR) imaging in an in vivo mouse model of inflammation. All animal experiments were approved according to animal welfare and local ethics committee regulations. An anti-murine E-selectin F(ab')2 monoclonal antibody, MES-1, was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Flow cytometry, Perl Prussian blue staining for iron, and MR imaging were performed by using Chinese hamster ovary (CHO) cells expressing mouse E-selectin to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO. Serial imaging was performed by using a 9.4-T MR imaging system with a custom receive-only coil. Tissue slices were stained to define distribution of E-selectin expression and localization of the MES-1-USPIO conjugate. MES-1-USPIO was shown to bind to CHO cells expressing mouse E-selectin in vitro. After injection of MES-1-USPIO in vivo, distinct changes in R2 relaxation rate (1/T2) characteristics were detected in inflamed ears when they were compared with control ears. Histologic analysis confirmed the vascular endothelial distribution of MES-1-USPIO. E-selectin expression in vivo can be selectively and directly imaged noninvasively with MR. This has the potential to be useful in the study of inflammatory disease.

304 Detection of Vascular Expression of E-Selectin in Vivo by Mr Imaging

Background: We aimed to develop a contrast agent suitable for targeting to E-selectin expressed on activated vascular endothelium in an in vivo model of inflammation and detection by magnetic resonance (MR) imaging.Methods: Anti-murine E-selectin F(ab')2 monoclonal antibody (mAb) (MES-1) was conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO). Flow cytometry, PERL staining for iron, and MR imaging were performed using CHO cells expressing mouse E-selectin (CHO-E) to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO, with serial imaging being performed using an Oxford/Varian 9.4T MR imaging system with a custom receive-only coil. Tissue sections were stained to define the distribution of E-selectin expression and the localisation of the MES-1-USPIO conjugate.Results: The MES-1-USPIO was shown to bind to CHO-E in vitro. Following injection of MES-1-USPIO in vivo, distinct changes in the R2 relaxation rate (1/T2) characteristics could be detected in inflamed ears compared to controls. Histological analysis confirmed the vascular endothelial distribution of the MES-1-USPIO.Conclusions: E-selectin expression in vivo can be selectively and directly imaged non-invasively with magnetic resonance. This molecular imaging tool has the potential to be useful for the diagnosis and monitoring of early or occult inflammation, and may provide an attractive alternative to established clinical investigations such as the use of radiolabelled leukocytes. In addition, such an agent may have value in the investigation of some solid tumours and metastases, either by targeting tumour-associated neovasculature or tumour cells expressing E-selectin.

α‐MSH and fragments: potential therapeutic agents in inflammation

α‐Melanocyte‐stimulating hormone (α‐MSH) exerts numerous immunomodulatory and anti‐inflammatory activities, which at least partly are mediated through the melanocortin receptor‐1 (MC‐1R), expressed on monocytes, dermal fibroblasts, dendritic cells (DCs), endothelial, and epithelial cells. Accordingly, α‐MSH downregulates the production of proinflammatory cytokines and the expression of costimulatory molecules on antigen‐presenting cells (APCs) via inhibiting the activation of transcription factors such as NF‐κB, while upregulating the production of suppressor factors such as IL‐10. Besides α‐MSH, its C‐terminal‐tripeptide KPV and the IL‐1β‐derived tripeptide KPT are capable of modulating APC functions. Using a mouse model of contact hypersensitivity (CHS), systemic and epicutaneous application of α‐MSH, KPV, or KPT inhibited CHS induction and induced hapten‐specific tolerance. However, using MC‐1R‐deficient mice (MC‐1Re/e), tolerance induction was found to be independent of MC‐1R expression. To further investigate the mechanisms responsible for tolerance induction, adoptive transfer experiments were performed. α‐MSH‐treated haptenized DCs inhibited CHS and induced hapten‐specific tolerance, via induction of regulatory T lymphocytes (Treg). In contrast, using a murine model of intestinal inflammation [Dextransulfate (DSS)‐induced colitis], the expression of a functional MC‐1R was found to be crucial for α‐MSH to exert its anti‐inflammatory activity; in wt mice, weight loss was reduced and the survival rate significantly was improved upon treatment with α‐MSH or KPV. However, DSS colitis was significantly aggravated in MC1‐Re/e mice, resulting in the death of all animals. Bone marrow transplantation from wt mice did not alter the course of inflammation, indicating that MC‐1R expression on non‐hematopoietic cells is crucial for host defense. These findings further support the therapeutic potential of α‐MSH‐related peptides for the treatment of inflammatory, autoimmune, and allergic diseases.

Blockade of the EGF Receptor Induces a Deranged Chemokine Expression in Keratinocytes Leading to Enhanced Skin Inflammation

During inflammatory skin disorders such as psoriasis, atopic dermatitis, and allergic contact dermatitis, epidermal keratinocytes overexpress large amounts of soluble epidermal growth factor receptor ligands in response to tumor necrosis factor alpha and interferon gamma. These cytokines also promote de novo synthesis of numerous chemokines, including CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL8/IL-8, in turn responsible for the recruitment of different leukocyte populations. This study demonstrates that stimulation of EGFR down-regulates CCL2, CCL5, and CXCL10, while it increases CXCL8 expression in keratinocytes. Conversely, EGFR signaling blockade produces opposite effects, with increased CCL2, CCL5, and CXCL10, and reduced CXCL8 expression. In a mouse model of contact hypersensitivity, a single topical administration of a selective EGFR kinase blocker before antigen challenge results in a markedly enhanced immune response with increased chemokine expression and heavier inflammatory cell infiltrate. Targeting EGFR on epithelial cells may thus have profound impact on inflammatory and immune responses.

New insights into the functions of alpha-MSH and related peptides in the immune system.

There is a substantial body of evidence that the tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) functions as a mediator of immunity and inflammation. The immunomodulating capacity of alpha-MSH is primarily because of its effects on melanocortin receptor (MC-1R)-expressing monocytes, macrophages, and dendritic cells (DCs). alpha-MSH down-regulates the production of proinflammatory and immunomodulating cytokines (IL-1, IL-6, TNF-alpha, IL-2, IFN-gamma, IL-4, IL-13) as well as the expression of costimulatory molecules (CD86, CD40, ICAM-1) on antigen-presenting DCs. In contrast, the production of the cytokine synthesis inhibitor IL-10 is up-regulated by alpha-MSH. At the molecular level, these effects of alpha-MSH are mediated via the inhibition of the activation of transcription factors such as NFkappaB. Not only alpha-MSH but also its C-terminal tripeptide (alpha-MSH 11-13, KPV) was able to bind to MC-1R and to modulate the function of APCs. In vivo, using a mouse model of contact hypersensitivity (CHS) systemic and topical application of alpha-MSH or KPV inhibited the sensitization and the elicitation phase of CHS and was able to induce hapten-specific tolerance. To investigate the underlying mechanisms of tolerance induction, we have performed in vivo transfer experiments. Treatment of naive mice with bone marrow-derived immature haptenized and alpha-MSH-pulsed DCs resulted in a significant inhibition of CHS. Furthermore, tolerance induction was found to be mediated by the generation of CTLA4(+) and IL-10-producing T lymphocytes. The potent capacity of alpha-MSH to modulate the function of antigen-presenting cells (APCs) has been further supported in another experimental approach. In vitro, by activating APCs, alpha-MSH has been shown to modulate IgE production by IL-4 and anti-CD40 stimulated B lymphocytes. Moreover, in a murine model of allergic airway inflammation, systemic treatment with alpha-MSH resulted in a significant reduction of allergen-specific IgE production, eosinophil influx, and IL-4 production. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to alpha-MSH treatment. Therefore, therapeutic application of alpha-MSH or related peptides (KPVs) as well as alpha-MSH/KPV-pulsed DCs may be a useful approach for the treatment of inflammatory, autoimmune, and allergic diseases in the future.

P–693 - Toxic effects of allopurinol on a contact hypersensitivity mouse model.

P–693 - Toxic effects of allopurinol on a contact hypersensitivity mouse model.

Allopurinol increases ear swelling and mortality in a dinitrofluorobenzene-induced contact hypersensitivity mouse model.

The immunomodulatory effects of allopurinol were investigated in a mouse contact hypersensitivity model. Allopurinol caused a time- and dose-dependent lethal effect in dinitrofluorobenzene (DNFB)-sensitized mice. Furthermore, allopurinol markedly increased ear swelling in the remaining mice. In contrast, TMX-67, a newly synthesized xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitor, had almost no effect on DNFB-sensitized mice. Allopurinol reduced both the spleen weight and white blood cell count in DNFB-sensitized mice without affecting the T cell subset of splenocytes. The production of interferon (IFN)-gamma, in the splenocytes of DNFB-sensitized mice was reduced by allopurinol administration. Death due to allopurinol was much lower in the non-sensitized mice than in the DNFB-sensitized mice. These findings indicate that allopurinol may interact with DNFB to enhance its toxicity and allopurinol might also modulate or enhance the inflammatory effect of DNFB. Also, DNFB may cause metabolic alterations via inflammation, leading to enhanced allopurinol toxicity.

Buspirone inhibits contact hypersensitivity in the mouse.

We have observed that 8-4-[4-2-pyrimidyl)-1-piperazinyl]butyl]-8-azaspiro [4.5]decane-7.9-dione, an agent commonly known as buspirone HCl, possesses immunosuppressive activity when administered either topically or systemically, as assessed in a mouse model of contact hypersensitivity. Topical or systemic administration of buspirone significantly reduced the tissue swelling and leukocyte infiltration associated with the elicitation phase of contact hypersensitivity. Buspirone is a safe, widely used drug which has a history of use in humans throughout the world. These data demonstrate a previously unknown pharmacologic activity of buspirone.