oxazolone and Drug-Hypersensitivity

Topics: Animals; Antibody Formation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Hypersensitivity; Estramustine; Humans; Hypersensitivity, Delayed; Killer Cells, Natural; Lymph Nodes; Male; Mice; Mitogens; Nitrogen Mustard Compounds; Oxazolone; Spleen; T-Lymphocytes; Thymus Gland; Time Factors

Cucurbitacin R is known to exhibit an anti-inflammatory effect in different experimental models of inflammation. In this article, we outline the effect of cucurbitacin R on T lymphocyte proliferation, cytokine production, and nuclear factor activation, as well as its influence on various experimental models of delayed-type hypersensitivity (DTH) in mice. Cucurbitacin R reduced the proliferation of phytohemagglutinin A-stimulated human T lymphocytes (IC(50), 18 microM), modifying the cell cycle, as well as the production of cytokines [interleukin (IL)-2, IL-4, IL-10, and especially interferon-gamma] and the induction of the principal cyclins implicated in the cell cycle (A(1), B(1), D(2), and E). These effects are brought on by a novel, selective inhibition of nuclear factor AT (NFAT) by cucurbitacin R, with no concomitant effect on other transcription factors such as activator protein-1. In addition, we tested the in vivo effects of cucurbitacin R in three experimental models of DTH, as well as its effects on T lymphocyte proliferation, the cell cycle, cytokines, and cyclins. Although cucurbitacin R was found to reduce the inflammatory response brought on by both oxazolone and dinitrofluorobenzene, its activity was even more pronounced against sheep red blood cell-induced edema in mouse paws, with a clear reduction in the production of IL-1beta, IL-4, and tumor necrosis factor alpha in the inflamed paw. In conclusion, cucurbitacin R has the potential to be a new immunosuppressive agent with antiproliferative effects through the inhibition of the NFAT with anti-inflammatory activity in DTH reactions.

Topics: Animals; Anti-Inflammatory Agents; Cell Cycle; Cell Proliferation; Cyclins; Cytokines; Dinitrofluorobenzene; Drug Hypersensitivity; Ear; Female; Foot; Humans; Hypersensitivity, Delayed; Intracellular Signaling Peptides and Proteins; Jurkat Cells; Mice; NFATC Transcription Factors; Oxazolone; T-Lymphocytes; Triterpenes

The murine popliteal lymph node assay (PLNA) was examined as a preclinical assay with the potential to identify low-molecular-weight compounds (LMWCs) that are likely to be associated with immune-mediated drug hypersensitivity reactions (IDHRs) in humans. We hypothesized that the contact sensitizer oxazolone (OX) would cause a strong PLN reaction in naive mice and that the PLN reaction would be attenuated in mice orally pretreated with OX due to the induction of oral tolerance. In naive mice, OX induced a strong PLN reaction and caused dose-dependent increases in PLN size, weight, cellularity, percentage of CD4(+) PLN T cells, and percentage of PLN B cells, with a concomitant decrease in the percentage of CD8(+) PLN T cells. Next, the PLNA was conducted in mice gavaged three times with either OX or vehicle alone (olive oil). Mice pretreated with OX had suppressed PLN reactions following the footpad injection of OX (decrease in PLN size, weight, and cellularity), which was associated with an increase in the percentage of PLN CD8(+)T cells. In contrast, oral pretreatment with OX had no observable effect on the PLN reaction induced following footpad injection of the irrelevant hapten dinitrochlorobenzene (DNCB). Adoptive transfer studies were conducted to examine the mechanism of PLN hyporesponsiveness. It was found that either (1) unfractionated splenocytes or (2) purified CD8(+) splenocytes, but not (3) purified CD4(+) splenocytes isolated from mice gavaged with OX adoptively transferred PLN suppression to naive BALB/c mice. Because OX is not a pharmaceutical, we also examined the NSAID diclofenac (DF) (Voltaren). Like OX, DF caused dose-dependent increases in PLN size, weight, and cellularity in naive mice. Furthermore, like OX, the diclofenac-induced PLN reaction was attenuated in mice that had been orally pretreated three times with DF. However, splenocytes from mice orally treated with DF were not able to adoptively transfer PLN hyporesponsiveness. Collectively, these observations demonstrate that both OX and DF are potent immunostimulators in the PLNA. As importantly, these results demonstrate that the immunostimulating potential of OX and DF in the PLNA is significantly decreased in mice orally exposed to the respective drug, possibly due to the presence of a cellular mechanism of oral tolerance. For OX, the mechanism appears to involve, in part, CD8(+) T cells, whereas the mechanism(s) associated with PLN hyporesponsiveness using DF remain to be def

Topics: Adjuvants, Immunologic; Administration, Oral; Adoptive Transfer; Animals; Anti-Inflammatory Agents, Non-Steroidal; CD8-Positive T-Lymphocytes; Diclofenac; Drug Hypersensitivity; Local Lymph Node Assay; Lymph Nodes; Mice; Mice, Inbred BALB C; Oxazolone; Spleen

To investigate the involvement of protease-activated receptor-2 (PAR-2) in allergic dermatitis, we generated PAR-2-deficient (PAR-2(-/-)) mice. Ear thickness, contact hypersensitivity (CH) induced by topical application of picryl chloride (PC) or oxazolone (Ox) after sensitization, and vascular permeability after ear passive cutaneous anaphylaxis (PCA) were compared between wild-type (WT) and PAR-2(-/-) mice. Ear thickness was almost the same in untreated WT and PAR-2(-/-) mice. Topical application of PC or Ox thickened the ears at 6, 24 and 48 h after challenge with a peak at 24 h in WT mice. In PAR-2(-/-) mice, the ear swelling induced by both PC and Ox was suppressed at every time point, and significant inhibition was found at 24 h in PC-induced CH and at 24 and 48 h in Ox-induced CH. Histopathological observation of the ears at 24 h after challenge revealed that PC- or Ox-induced ear edema and infiltration of inflammatory cells in WT mice were greatly attenuated in PAR-2(-/-) mice. The vascular permeability in the ears after PCA was not different between WT and PAR-2(-/-) mice. These results strongly suggest that PAR-2 plays a crucial role in type IV allergic dermatitis but not in type I allergic dermatitis.

Topics: Adjuvants, Immunologic; Animals; Dermatitis, Allergic Contact; Disease Models, Animal; Drug Hypersensitivity; Ear; Gene Deletion; Male; Mice; Mice, Knockout; Microscopy; Oxazolone; Picryl Chloride; Receptor, PAR-2; Receptors, Thrombin; Staining and Labeling; Time Factors

The inhibitory effects of tea catechins, the O-methylated derivatives of (-)-epigallocatechin-3-O-gallate (EGCG), and the polyphenol extracts from tea leaves (Camellia sinensis L.) on oxazolone-induced type IV allergy in male ICR mice were investigated. Four major tea catechins and two O-methylated derivatives, (-)-epigallocatechin-3-O-(3-O-methyl)gallate (EGCG3' 'Me) and (-)-epigallocatechin-3-O-(4-O-methyl)gallate (EGCG4' 'Me), showed significant inhibitory effects on mouse type IV allergy after a percutaneous administration at a dose of 0.13 mg/ear. Among tea catechins, the compounds including galloyl moieties, such as EGCG and (-)-epicatechin-3-O-gallate (ECG), showed the strongest inhibitory activities on mouse type IV allergy. The inhibitory activities of EGCG3' 'Me and EGCG4' 'Me were higher than that of EGCG at a dose of 0.05 mg/ear. Polyphenol extract from tea leaves of Benihomare cultivar, which includes EGCG3' 'Me, strongly inhibited mouse type IV allergy after percutaneous administration in comparison with that from Yabukita cultivar, which does not include EGCG3' 'Me, at doses of 0.05 and 0.13 mg/ear. EGCG3' 'Me is thought to contribute, at least in part, to the inhibitory ability of Benihomare tea leaves on mouse type IV allergy. EGCG and the polyphenol extracts from Benihomare and Yabukita tea leaves also inhibited mouse type IV allergy by oral administration at 1 h before the sensitization and at 1 h before the challenge with oxazolone. Therefore, daily intake of tea drinks could have potential to prevent type IV allergy.

Topics: Administration, Topical; Animals; Catechin; Drug Hypersensitivity; Flavonoids; Male; Mice; Mice, Inbred ICR; Oxazolone; Phenols; Plant Leaves; Polymers; Species Specificity; Tea

We have examined in a murine model, the potential of the oral mucosa (OM) to serve as inductive and/or expression site(s) of delayed-type hypersensitivity (DTH) reactions. The expression of DTH reactions in the murine buccal mucosa was studied after topical application of oxazolone or picryl chloride onto the OM of animals previously sensitized with either hapten. Irrespective of the site of priming (skin or buccal mucosa), inflammatory cells appeared in the OM following buccal elicitation with the pertinent hapten. The density of infiltrating cells peaked at 24 h after hapten elicitation. Such inflammatory reactions, which comprised mainly mononuclear cells at 24 h, were preceded by an early inflammatory reaction that developed only in animals previously sensitized at skin sites. This early reaction, comprising mainly PMN neutrophils, peaked at 6-8 h, declined by 8-16 h, and was not observed in mice previously sensitized in the buccal mucosa. The 24 h reactions failed to develop in nude mice similarly treated, in intact unsensitized mice, as well as in animals sensitized with an irrelevant hapten. These reactions could be adoptively transferred to naive animals by LN cells but not by serum from sensitized syngeneic donors. Furthermore, LN cell suspensions depleted of T cells failed to transfer sensitization for subsequent OM DTH. Topical application of contact sensitizing haptens onto OM induced priming for subsequent DTH reactions elicited with recall antigen applied at a distant skin site or at a local buccal site. These results demonstrate that the OM has the capacity to serve both as an inductive and as an expression site for T cell-mediated inflammatory reactions, be these expressed or induced at local mucosal sites or at remote systemic (skin) sites. This animal model should be valuable for studying the regulation of T cell-mediated inflammatory responses at mucosal surfaces.

Topics: Administration, Buccal; Administration, Cutaneous; Animals; Cell Count; Cell Movement; Disease Models, Animal; Drug Hypersensitivity; Female; Hypersensitivity, Delayed; Immunity, Cellular; Immunotherapy, Adoptive; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mouth Mucosa; Oxazolone; Picryl Chloride; T-Lymphocytes

2,4,6-Trinitrochlorobenzene (picryl chloride) and 2,4-dinitrochlorobenzene (DNCB) fail to cross-sensitize with respect to contact sensitivity in mice. Nevertheless, topical exposure of mice to DNCB and other skin-sensitizing dinitrobenzene derivatives was found to result in a significant impairment of draining lymph node cell proliferative responses induced following epicutaneous challenge with picryl chloride 5 days later. The inhibition of picryl chloride induced proliferation was associated with an impairment of contact sensitization to this chemical. The effect of DNCB on subsequent responses to picryl chloride was transient and no longer detectable 15 days following exposure. The inhibition of proliferation and contact sensitization caused by DNCB was largely restricted to picryl chloride. Thus, DNCB failed to influence the development of contact allergy to the unrelated chemical 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone) and exerted a far less pronounced effect on oxazolone-induced proliferative responses. These data, therefore, describe an antigen-restricted form of antigenic competition which is associated with a depression of the primary lymphocyte proliferative response.

Topics: Animals; Cross Reactions; Dinitrochlorobenzene; Drug Hypersensitivity; Epitopes; Lymphocyte Activation; Mice; Oxazolone; Picryl Chloride; Premedication; Time Factors

Topics: Animals; Drug Hypersensitivity; Edema; Female; Hypersensitivity, Delayed; Kinetics; Mice; Mice, Inbred BALB C; Oxazoles; Oxazolone; Peroxidase

Exposure of mouse skin to UV radiation in doses comparable to those commonly received by humans has been shown to diminish the capacity of irradiated skin to mediate the induction of contact hypersensitivity to dinitrofluorobenzene (DNFB). In other studies, contact sensitization reactions to the structurally related hapten, trinitrochlorobenzene (TNCB), have been used to test the immunogenic properties of haptenated subpopulations of epidermal cells. To extend the applicability of TNCB to experiments that examine UVB modulation of immunization by epidermal cells, we examined the sensitivity of TNCB-induced contact hypersensitivity to low doses of UVB radiation. Abdominal skin of C3H mice was exposed to daily doses of 660 J/m2 broad-band UV radiation for 4 successive days. Immediately following the final exposure, 7% TNCB was applied to irradiated or non-irradiated skin of designated mice. After 5 days, mice were ear-challenged with 2% TNCB, and incremental ear-swelling responses were measured. Mice sensitized with TNCB through irradiated skin exhibited significantly diminished responses compared with UVB-treated mice sensitized through non-irradiated skin. We also found that mice initially sensitized with TNCB through irradiated skin but subsequently painted with oxazolone on normal skin developed full responses to ear-challenge with oxazolone. In contrast, mice sensitized initially with TNCB through irradiated skin failed to fully immunize even after TNCB was repainted on normal skin at a later date. We conclude that low-dose UVB radiation interrupts the induction of contact hypersensitivity to TNCB, leading to hapten-specific nonresponsiveness rather than hypersensitivity, and that this capacity to prevent successful immunization with TNCB is limited to the site of irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Animals; Dose-Response Relationship, Radiation; Drug Hypersensitivity; Epidermis; Female; Hypersensitivity, Delayed; Immune Tolerance; Mice; Mice, Inbred C3H; Oxazolone; Picryl Chloride; Ultraviolet Rays

In the present study, immunopharmacological effects of clonidine-TTS on allergic contact dermatitis (ACD) to non-related, established contact sensitizers were investigated in guinea pigs. First, to evaluate the hypotensive effect of clonidine-TTS in guinea pigs, intra-arterial blood pressure was recorded. After 4 days of treatment with one (or two) TTS per animal, a reduction of arterial blood pressure from 71 +/- 1 to 51 +/- 2 mm Hg was observed. We subsequently assessed the effects of clonidine-TTS on contact hypersensitivity reactions to 2,4-dinitrochlorobenzene (DNCB) and 4-ethoxymethylene-2-phenyl-oxazolone (Ox). This study indicates that clonidine-TTS suppressed the elicitation of contact hypersensitivity reactions. The observed immunosuppressive effect of clonidine may account for the relatively weak hypersensitivity reactions to this drug in experimental animal studies. Further studies are needed to determine whether such findings are of relevance to the clinical use of clonidine in patient populations.

Topics: Administration, Cutaneous; Animals; Blood Pressure; Clonidine; Dermatitis, Contact; Dinitrochlorobenzene; Drug Hypersensitivity; Female; Guinea Pigs; Oxazolone

The effects of mast cell activation/degranulation on the elicitation of contact sensitivity (CS) to oxazolone and dinitrofluorobenzene were investigated. Mice were actively sensitized to oxazolone by epicutaneous painting followed by ear challenge. Passive sensitization to DNFB was induced by intradermal injections of dinitrophenol (DNP)-specific cloned T cells in the ears. Mast cells in the challenged ears were activated in various time periods by inducing a passive cutaneous anaphylaxis reaction where passive sensitization with monoclonal IgE anti-DNP antibodies was followed by iv injection of DNP-BSA. This combination of immediate and delayed-type hypersensitivity reactions resulted in a significant increase of ear swelling without any noticeable effect on cellular infiltration when the contact response was evaluated a short time (3-4 hr) after mast cell activation. The very same results were obtained in naive (unsensitized) mice, indicating that this reaction was nonspecific. However, when the CS reaction was evaluated at its peak, i.e., 24 hr post challenge, mast cell activation that had been induced 0.5-11 hr after ear challenge did not have any significant effect on both swelling and cellular infiltration when the latter was evaluated by a radiometric assay. We conclude that in these systems mast cell activation/degranulation makes little or no contribution to the modulation of T-cell activity.

Topics: Animals; Dermatitis, Contact; Dinitrofluorobenzene; Drug Hypersensitivity; Exocytosis; Female; Histamine Release; Immunoglobulin E; Mast Cells; Mice; Mice, Inbred BALB C; Oxazolone; Passive Cutaneous Anaphylaxis; T-Lymphocytes

In previous studies, the alpha 2-adrenoceptor agonist clonidine has been shown to suppress the wheal and flare reaction in guinea pigs sensitized to ovalbumin. This phenomenon has been further studied with special reference to effects on the dermal inflammatory cell infiltrate and mast cells. Clonidine lessens the degranulation of mast cells seen in control untreated immediate hypersensitivity reactions. Less neutrophils and eosinophils arrive to the treated reactions. Basophils and mononuclear cells (chiefly lymphocytes) which characterize the late phase of the wheal and flare reaction were not influenced by clonidine. Clonidine had a possible minimal effect on allergic contact (delayed hypersensitivity) reactions. The toxic contact reaction to croton oil (nonspecific cutaneous inflammation) was not affected.

Topics: Animals; Cell Movement; Clonidine; Croton Oil; Dermatitis, Contact; Drug Hypersensitivity; Female; Granulocytes; Guinea Pigs; Histamine; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Inflammation; Mast Cells; Ovalbumin; Oxazolone; Skin; Skin Tests

The effect of whole-body irradiation on cellular immunity, as measured in vivo by delayed-type hypersensitivity (DTH) to oxazolone (4- ethoxymethylene -2-phenyl- oxazol -5-one), was determined in CD2F1 mice. DTH, determined by changes in ear swelling after challenge with oxazolone, was significantly depressed in irradiated mice (500-900 rad of 60Co) in a dose-dependent fashion when animals were irradiated after sensitization and before challenge with oxazolone. Administration of WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] 30 min before irradiation (2 days after sensitization) resulted in protection against suppression of DTH, which was dependent on drug and radiation dose. An effective dose of WR-2721 (200 mg/kg body wt) provided an approximate dose-modifying factor of 1.3. The data suggest that WR-2721 interacts with cells involved in that DTH response (lymphocytes and/or macrophages) and that WR-2721 may be useful in protecting against radiation-induced decrements in cell-mediated immunity.

Topics: Amifostine; Animals; Cobalt Radioisotopes; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Hypersensitivity; Hypersensitivity, Delayed; Immune Tolerance; Immunity, Cellular; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Organothiophosphorus Compounds; Oxazoles; Oxazolone; Time Factors; Whole-Body Irradiation

It has been suggested that reserpine blocks expression of delayed hypersensitivity in mice because it depletes stores of the vasoactive amine serotonin in mast cells. To determine whether mast cell serotonin or other mast cell-derived mediators are essential for delayed hypersensitivity, responses to contact sensitizers in mast cell-deficient W/Wv or Sl/Sld mice were studied. Because blood platelets represent another potential source of serotonin in delayed hypersensitivity responses, beige mice, whose platelets contain less than 1 percent of the normal levels of serotonin, were also examined. By the criteria of tissue swelling, infiltration of iodinated leukocytes, or histology, mast cell-deficient or beige mice expressed delayed hypersensitivity reactions whose intensity generally equaled or exceeded that of reactions in littermate controls. In addition, reserpine blocked delayed hypersensitivity in W/Wv and beige mice, suggesting that effects on mast cell or platelet serotonin cannot explain this drug's action in delayed hypersensitivity.

Topics: Animals; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Mast Cells; Methysergide; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Oxazolone; Reserpine; Serotonin

Acute and delayed hypersensitivity reactions were compared in mice fed diets low in copper (less than 20 mumol copper kg-1) or adequate (more than 300 mumol copper kg-1) for seven to nine weeks after weaning. In the copper depleted animals there was a significant enhancement (P less than 0.01) of histamine-induced paw oedema measured 15 minutes after challenge. The variance of responses within the two dietary groups was similar. Delayed contact hypersensitivity reactions to oxozalone were also significantly increased (P less than 0.01) in the deficient mice. In this study there were some signs of differences in variance heterogeneity but they were statistically insignificant. Delayed-type hypersensitivity to sheep erythrocytes was similarly but less markedly (P less than 0.05) affected. Group differences just failed to reach statistical significance after logarithmic transformation (P less than 0.07) or non-parametric analysis (P less than 0.06). At challenge, the copper deficient mice had a significant (P less than 0.05) plasma hypercholesterolaemia. A few individuals also showed signs of spleen enlargement and mild haemoglobinaemia but otherwise the animals appeared clinically normal and were similar in weight to the controls. Plasma (P less than 0.001), erythrocyte (P less than 0.01) and liver (P less than 0.01) copper concentrations were significantly reduced in the copper-depressed mice, although the concentrations of copper and zinc in the spleen were increased (P less than 0.05) in the same group. Whole blood superoxide dismutase activity was also significantly decreased (P less than 0.01) but erythrocyte glutathione peroxidase activities were similar in both groups, as were blood and liver zinc concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animal Feed; Animals; Body Weight; Copper; Drug Hypersensitivity; Female; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Mice; Mice, Inbred Strains; Organ Size; Oxazolone; Trace Elements

This report describes IgM, IgG and IgE antibody and contact sensitivity responses of strains of mice congenic at the major histocompatibility complex (MHC) to skin painting with picryl chloride or oxazolone. B10 had low responses of all classes to picryl chloride. This was also reflected by the DNA synthesis occurring in their draining lymph nodes after painting. B10BR were high responders to picryl chloride for all classes but B10A and B10D2 were high responders for all classes except IgE. This presents evidence that genes in the MHC can selectively control antibody classes. The contact sensitivity response of the congenics to oxazolone confirmed the low previously described responsiveness of B10 mice. Antibody responses to oxazolone (agglutinin and reagin) were low for all congenics with B10 backgrounds.

Topics: Agglutinins; Animals; DNA; Drug Hypersensitivity; Genes, MHC Class II; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Major Histocompatibility Complex; Male; Mice; Mice, Inbred Strains; Oxazolone; Picryl Chloride; Reagins

The depression of contact sensitivity to oxazolone in mice infected with Pseudomonas aeruginosa was studied. In oxazolone-sensitized mice, P. aeruginosa infection affects cell proliferation in the lymph nodes draining the site of sensitization. This impaired cell proliferation does not seem to be due to an altered lymphocyte reactivity, since lymph node and spleen cells from infected animals show a normal mitotic responsiveness to both T and B cell mitogens. In addition, the draining lymph nodes and spleens of mice exhibiting a depressed response to oxazolone contain a cell population able actively to suppress the response to the same antigen of syngeneic recipients sensitized immediately before the cell transfer. These suppressor cells require antigenic stimulation and appear to act on the induction phase of contact sensitivity.

Topics: Animals; DNA; Drug Hypersensitivity; Female; Hypersensitivity, Delayed; Immunization; Lymphocyte Activation; Lymphocytes; Male; Mice; Oxazolone; Pseudomonas Infections; T-Lymphocytes, Regulatory

The cellular basis of depression of contact sensitivity to oxazolone in mice injected with Pseudomonas aeruginosa was studied. Cells from draining lymph nodes of mice sensitized with oxazolone 18 h previously were able to induce contact sensitivity to normal mice when administered in their footpads. In contrast, cells from draining lymph nodes of P. aeruginosa-injected and oxazolone-sensitized donors failed to induce contact sensitivity when injected in the footpad of normal mice and were capable of actively blocking the immunizing process brought about by lymph node cells from sensitized mice when injected together in the footpad of normal recipients. The P. aeruginosa-induced suppressor cells required antigenic stimulation, had precursors sensitive to cyclophosphamide, and did not affect the effector mechanisms of contact sensitivity. Thus, the results suggest that P. aeurginosa depresses contact sensitivity to oxazolone by enhancing the activity of suppressor cells which normally arise during the sensitization process and which affect the afferent limb of the immune response, probably by inhibiting the normal recruitment of T lymphocytes in the draining lymph nodes.

Topics: Animals; Antigens, Bacterial; Cell Division; Cyclophosphamide; DNA; Drug Hypersensitivity; Female; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Oxazolone; Pseudomonas aeruginosa; T-Lymphocytes, Regulatory

Oxazolone-sensitized mite-infested (SWR-M) and mite-free (SWR-J) mice were challenged with oxazolone on the skin of the neck and shoulder. The migration of radioactively labeled cells to the site of contact sensitivity reaction to oxazolone was significantly less in SWR-M than in SWR-J mice. Serum obtained from SWR-M mice suppressed the extravasation of cells into the skin site of SWR-J mice challenged with oxazolone. The decrease in cellular influx in SWR-M mice occurred in areas of mite infestation (skin of neck and shoulder) as well as in areas not infested with mites (the ears). SWR-M mice also gave evidence of enhanced vascular permeability. A possible role for histamine in the inhibition of contact sensitivity in mite-infested mice is discussed.

Topics: Animals; Capillary Permeability; Drug Hypersensitivity; Female; Hypersensitivity, Delayed; Male; Mast Cells; Mice; Mite Infestations; Oxazolone

The potency of cytostatic and anti-inflammatory drugs was tested on the oxazolone-induced cutaneous basophil hypersensitivity (CBH) in mice. The challenge reaction was performed early after sensitization in order to minimize B-cell expression; exudative and cellular infiltration was estimated 6 h, 24 h and 48 h after challenge. The potency of drugs was tested at three different periods of immunization: 2 days before or after sensitization or before challenge. Cytostatics act mainly when cells are being committed, a corticoid acts on inflammation linked to committed cells, NSAIDs show inconstant anti-inflammatory effects on this test. D-Penicillamine and levamisole act in the same depressive profile in normal animals. Thus the CBH model appears to be relevant in studying drug activities on inflammation linked to T-cell expression.

Topics: Animals; Anti-Inflammatory Agents; Basophils; Drug Hypersensitivity; Hypersensitivity, Delayed; Immunosuppressive Agents; Male; Mice; Oxazoles; Oxazolone; Skin; Time Factors

Contact hypersensitivity to dinitrochlorobenzene (DNCB), picryl chloride (PCl) or oxazolone was induced in mice by skin painting with these agents, and was measured by skin testing in vivo using the ear swelling method. Prior administration of dinitrobenzene sulfonate (DNBS) or picryl sulfonic acid prevented sensitization to DNCB and PCl, respectively. Both this tolerization and the original sensitization were specific for the hapten used. Cyclophosphamide given before sensitization enhanced skin reactions, but when given before tolerization it interfered with establishment of tolerance. Cells from both sensitized and tolerized mice were shown to be reactive with the corresponding haptens in vitro in the leukocyte adherence inhibition (LAI) reaction. LAI specificity was similar to that found for cutaneous reactivity. The reaction of DNCB-sensitized cells with DNBS led to the production of a soluble mediator which induced LAI in normal cells. The demonstration of potentially reactive cells in mice judged to be tolerant by skin testing indicates the concomitant existence of suppressor factors.

Topics: Animals; Cell Adhesion; Cyclophosphamide; Dermatitis, Contact; Dinitrochlorobenzene; Drug Hypersensitivity; Female; Hypersensitivity, Delayed; Immune Tolerance; Immunity, Cellular; Leukocytes; Mice; Oxazolone; Picryl Chloride; Skin Tests

The effect of levamisole upon cell-mediated immunity was investigated using the oxazolone-induced contact sensitivity response in immunosuppressed and nonimmunosuppressed C57Bl male mice. Mice were sensitized to oxazolone on day 0, and where appropriate, methotrexate (1 mg/kg, p.o.) was administered on days 1 and 2. On day 3, levamisole (5--50 mg/kg, p.o., base) was administered. One hour later, the animals were challenged with oxazolone on the left hindpaw. Twenty-four hours after challenge, the resulting edema was read plethysmographically. Levamisole, in the absence of immunosuppression, had no significant effect upon the oxazolone response whereas, in the face of immunosuppression, restoration of oxazolone responsiveness was observed. These results were suggested to be due to (1) the ability of levamisole to stimulate opposing suppressor and effector components of the oxazolone response coupled with (2) an apparent alteration of suppressor influence by methotrexate allowing levamisole to enhance an unencumbered effector cell population.

Topics: Animals; Drug Hypersensitivity; Immunity, Cellular; Immunosuppression Therapy; Levamisole; Male; Methotrexate; Mice; Mice, Inbred C57BL; Oxazolone

Chickens can easily be induced to develop delayed-type skin reactions to oxazolone when animals are sensitized 7 days before the challenge. The reaction is quantitated by assessing the increase in wattle thickness: maximum reactions occur 24 h after challenge. The reaction is inhibited by neonatal thymectomy or bursectomy; these findings therefore suggest also an important B-derived component in delayed hypersensitivity to oxazolone.

Topics: Animals; Bursa of Fabricius; Chickens; Dermatitis, Contact; Drug Hypersensitivity; Hypersensitivity, Delayed; Male; Oxazolone; Thymus Gland