Rejection of dinitrochlorobenzene-conjugated syngeneic tumor cells by dinitrochlorobenzene-sensitized guinea pigs.
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Dinitrochlorobenzene responsivity: difference between patients with severe pulmonary coccidioidomycosis and patients with disseminated coccidioidomycosis.
Immunologic responses in 15 patients with severe pulmonary coccidioidomycosis and in 50 patients with disseminated coccidioidomycosis were measured by determination of complement-fixing (CF) antibody titers to coccidioidin in serum, coccidioidin (1:100) skin tests, and sensitization to dinitrochlorobenzene. Among the patients with desseminated coccidioidomycosis, the nine with CF antibody titers of less than or equal to 1:8 had normal responses to dinitrochlorobenzene, but the 41 with titers of greater than or equal to 1:16 had responses that were significantly lower than those of controls (P less than 0.001). In contrast, all patients with severe pulmonary coccidioidomycosis had CF antibody titers of greater than or equal to 1:16 and had responses to dinitrochlorobenzene that were greater (but not significantly greater) than those of controls. Among subjected with antibody titers of greater than or equal to 1:16, responsiveness to coccidioidin was found in 27% of those with severe pulmonary disease and in 39% of those with disseminated disease. Thus impaired responsivity to dinitrochlorobenzene in coccidioidomycosis is restricted to patients who have disseminated illness and high titers of CF antibody and is separable from lack of responsiveness to coccidioidin.
Antibodies, Fungal↗
[Reproduction of amyloidosis in mice by contact sensitization with dinitrochlorobenzene].
Induction of murine amyloidosis by contact sensitization with hapten--dinitrochlorobenzene is described. Three to five applications of 15--25% dinitrochlorobenzene solution in acetone during two weeks are necessary for this. Within 3 weeks after the 1st application amyloidosis develops involving consecutively the spleen, liver, kidney and heart. Such consequence of the organ involvement and tinctorial pecularities are typical of murine amyloidosis.
Amyloidosis↗
Bacillus Calmette-Guérin and dinitrochlorobenzene immunotherapy of chemically induced bladder tumors.
Immunologic incompetence is correlated with increased susceptibility to malignacy. Immunostimulation with such agents as Bacillus Calmette-Guérin (BCG) and dinitrochlorobenzene (DNCB) have resulted in regression of cutaneous maligancies. An evaluation of the effect of BCG and dinitrochlorobenzene sensitization and bladder irrigation in Fischer rats revealed no decrease in the incidence of bladder tumors induced by 2-formylamino-4-(5-nitro-2-furyl) thiazole (FANFT). However, direct intralesional injection of BCG into early bladder tumors was effective in preventing the progression of such tumors in seven of ten BCG-sensitized rats (P less than 0.005). No effect was seen when BCG was injected intralesionally in unsensitized rats or when control solutions were injected.
Animals↗
[Basophils in the infiltrate of guinea pig experimental contact dermatitis. Dinitrochlorobenzene and citraconic anhydride (author's transl)].
We observed, in addition to the lymphocytes of the classical descriptions, large numbers of basophils in the infiltrate of the specific sensitization reaction with dinitrochlorobenzene and citraconic acid, a few eosinophils in the reaction with dinitrochlorobenzene and rather more eosinophils in the reaction with citraconic acid.
Animals↗
Intralesional treatment of recurrent metastatic cutaneous malignant melanoma: a randomized prospective study of intralesional Bacillus Calmette-Guerin versus intralesional dinitrochlorobenzene.
Eighteen patients with multiple recurrences of malignant melanoma without evident distant spread were randomly assigned to treatment with either intralesional Bacillus Calmette-Guerin (BCG) or intralesional dinitrochlorobenzene (DNCB). Both agents were able to destroy approximately 90% of the injected intradermal nodules. Intradermal disease was more easily obliterated than subcutaneous disease with intralesional treatment with either agent, and local control of satellitosis with elimination of all clinically evident tumor was achieved in the patients who had intradermal without subcutaneous satellitosis, regardless of whether the patient was receiving BCG or DNCB. The clinical courses of the treated patients were essentially the same. Although PHA reactivity was depressed, the patients in both groups were responsive to recall and melanoma skin test antigens, demonstrated leukocyte migration inhibition with melanoma antigen and were generally within normal limits when assayed for 29 degrees C E rosettes. Our study demonstrated a dramatic difference in toxicity between the two intralesional agents without a similar difference in therapeutic efficacy or immune testing.
Adult↗
Differing mechanisms of tolerance and desensitization to dinitrochlorobenzene in guinea pigs.
In the present paper the mechanisms of tolerance and desensitization to dinitrochlorobenzene (DNCB) contact sensitivity in guinea pigs were investigated using the methods of adoptive sensitization of tolerant and normal syngeneic recipients and cyclophosphamide-treatment of tolerant animals known to selectively inactivate suppressor lymphocytes. It was shown that desensitization of presensitized animals is caused by the direct effect of the intravenously injected hapten on the effector cells in the peripheral compartment. The immediate onset of unresponsiveness and its very short duration almost exclude the possible involvement of enhancing antibodies or suppressor cells. In the case of tolerance induced by pretreatment with dinitrobenzenesulfonic acid, suppressor cell activity is enhanced, preventing normal specific immunocompetent cells from recognizing the antigen and/or proliferating in the draining lymph nodes. Whether suppressor lymphocytes are of the B or T type is not yet known.
Animals↗
Ultrastructural morphometry of blastogenesis I: transformation of small lymphocytes stimulated in vivo with dinitrochlorobenzene.
Changes in the volumes and surfaces of subcellular compartments of unstimulated small lymphocytes and immunoblasts in mouse axillary lymph nodes have been established using stereological techniques. Blast transformation was induced in vivo with dinitrochlorobenzene (DNCB). Cell samples were obtained by random sampling regimes applied at light and electron microscopic levels. From electron micrographs the volume densities of euchromatin, heterochromatin, nucleoli, mitochondria, Golgi apparatus and rough endoplasmic reticulum were determined. Cell surface/volume ratios were also computed. By estimating mean nuclear volumes using light microscopy, it was possible to calculate absolute compartmental volumes and to evaluate the plasma membrane surface areas of average cells. Transformation in this model was characterized by a considerable cellular hypertrophy and a substantial increase in plasmalemma surface. Hypertrophy was the consequence of increases in the volumes of all measured intracellular compartments, notably euchromatin and "residual cytoplasm" (including ground cytoplasm and free ribosomes). These changes are discussed in the context of the altered metabolic status of cells.
Animals↗
A new method for obtaining viable cells from dermal infiltrates. A study on 2,4 dinitrochlorobenzene induced contact dermatitis.
Experimental contact dermatitis has been induced in 2,4 dinitrochlorobenzene (DNCB) sensitized guinea pigs. The developing dermal infiltrate was excised and the infiltrating cells were obtained by mechanical extraction alone as well as by the combination with collagenase and elastase treatment. The most viable cells appeared in the elastase and mechanically extracted samples and the least in those subjected to mechanical treatment alone. The most cells in the enzyme-treated samples were present 24 h after re-exposure of the sensitized animals to DNCB consisting mainly of lymphocytes and of polymorphonuclear granulocytes. The optimum conditions for the action of enzymes including optimum duration of the treatment, buffer milieu, aspecific proteolytic effect on foreign substrate and action on T and B cell receptors have been elaborated. It was concluded that 80 min of collagenase treatment with gentle mechanical extraction under specified conditions does not affect any measurable immunologic properties of the liberated cells resulting in the second best yield. A comparison of these data with earlier reports and their significance is being discussed.
Animals↗
Tuberculin and dinitrochlorobenzene (DNCB) tests in cancer patients before and after cytostatic drug therapy.
In 137 patients with different kinds of cancer and different cancer stage, cell-mediated immunity was investigated by DNCB (dinitrochlorobenzene) and tuberculin test. These two skin tests were performed before and after cytostatic drug combination therapy. For a collective of cancer patients we found a positive correlation between skin reactions and prognosis and a negative correlation between skin reactions and cancer stage. After cytostatic drug therapy skin reactions could be significantly stronger. This could be observed in 50% when one test was positive before chemotherapy and in only 20% when both tests were negative before chemotherapy. There existed a significant correlation between an increased reaction after cytostatic drug therapy and objective tumor regression. When skin reactions decreased, tumor progression was seen in all cases. Due to these observations we use skin reactions as a good parameter for therapy results. When delayed cutaneous hypersensitivity impairs 2--3 weeks after chemotherapy, we then change the cytostatic drug combination immediately. We cannot say at this moment, whether an improvement of cytostatic drug therapy can be reached in this way.
Cyclophosphamide↗
Integrated Multi-omics Profiling of 2,4-dinitrochlorobenzene (DNCB)-induced Atopic Dermatitis in Mice Reveals a Coordinated Network of Barrier Dysfunction, Immune Activation, and Metabolic Reprogramming.
Atopic dermatitis (AD) is caused by a combination of epidermal barrier defect and immune imbalance. However, the molecular networks between these structural abnormalities and metabolic variations are unclear. This study aim of this research was to examine the concurrent molecular alterations in skin barrier damage and metabolic disorders in an AD-like mouse model by a multi-omics strategy. A 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model was established and the skin tissues were examined through the combination of transcriptomic, quantitative proteomic, and metabolomic analyses. Cross-omics correlation and network analyses were performed to identify consistently abnormal molecular pathways and crucial regulatory molecules. DNCB treatment caused severe epidermal hyperplasia, and prominent infiltration of CD3⁺ T cells, F4/80⁺ macrophages, and mast cells. Transcriptomic and proteomic analysis indicated significant disruption in keratinocyte differentiation, extracellular matrix organization, and cornified envelope formation pathways. Combined analysis detected 171 molecules which were simultaneously altered at both mRNA and protein levels, and network analysis identified FLG2 and KRT6B as central barrier-related molecules. Pathway enrichment analysis consistently showed the participation of AMPK and PPAR signaling pathways. Metabolomic analysis also revealed coordinated changes in lipid and amino acid metabolism which were closely associated with cornified envelope-associated genes and collagen-modifying enzymes. These findings indicate a close relationship between barrier, immune and metabolic regulation in DNCB-induced dermatitis and provide a multi-omics resource for future mechanistic studies of atopic skin inflammation.
Animals↗
A nephropathy occuring in rats treated with dinitrochlorobenzene and N-methyl-N-nitroso guanidine.
Chronic administration of a potent oral carcinogen N-Methyl-N-Nitroso guanidine (M.N.N.G.) failed to produce gastric carcinoma in CFHB Wistar rats sensitised to 2.4 dinitrochlorobenzene (D.N.C.B.). In addition animals receiving both D.N.C.B. alone and D.N.C.B. and M.N.N.G. developed a severe nephropathy characterised by heavy proteinuria and extensive renal cortical damage. The histological features include proliferation of parietal epithelial cells and mesangial sclerosis. An association between the nephropathy and long term D.N.C.B. administration is suggested and on the basis of investigation to date direct toxicity rather than immune complex disease seems more likely.
Animals↗
Immune reactivity of women on hormonal contraceptives: dinitrochlorobenzene sensitization test and skin reactivity to irritants.
To evaluate the influence of sex steroids on immunity in 87 women on hormonal contraceptives, sensitization tests were performed with the contact allergen, 2,4-dinitrochlorobenzene (DNCB). Forty-five women were taking oral contraceptives of combined oestrogen/progestogen of the same brand (low oestrogenic and middle range progestogenic activity); 27 had received intramuscular injections of medroxyprogesterone acetate and 15 women were using a sequential pill. The results were compared with those of 44 women not taking contraceptive steroids and matched for age. In women on the combined pill and those who had received intramuscular progesterone, the mean DNCB reactivity was significantly increased (0.02 less than p less than 0.05 and 0.001 less than p less than 0.01, respectively), whereas women using a sequential pill proved to show a decreased skin reactivity in the oestrogenic phase of this pill. (p = 0.05). The changes observed proved to be specific, since no statistically significant differences in overall skin reactivity to irritants between the four groups of women could be observed. The clinical implications of these results have been considered.
Adolescent↗
Dinitrochlorobenzene sensitisation test in women on hormonal contraceptives.
Cell-mediated immunity was measured in women on hormonal contraceptives using the 2,4-dinitrochlorobenzene (D.N.C.B.) sensitisation test. Three groups of women were studied: forty-eight women were taking oral contraceptives of combined oestrogen/progestogen (thirty-seven of them had used oral contraceptives for a year or longer); twelve women were using a sequential pill (ethinyloestradiol and megestrolacetate); and sixteen women had received intramuscular injections of medroxyprogesterone acetate. The results were compared with those of a control group of twenty-nine age-matched women not taking contraceptive steroids. In women on the combined contraceptive pill and those who had received intramuscular progesterone, mean D.N.C.B. reactivity was significantly increased. The results were even more striking in women who had used combined contraceptive pills for more than one year. These results do not accord with the previously reported decrease in cell-mediated immunity in women on hormonal contraceptives.
Adolescent↗
In-vitro monitoring of cell-mediated immunity to dinitrochlorobenzene.
A dinitrochlorobenzene (D.N.C.B.)/red-blood-cell conjugate inhibited migration of leucocytes which came from D.N.C.B. sensitised patients. This effect provided the basis for a rapid, sensitive, and quantitative in-vitro measure of D.N.C.B. sensitivity. Frequent serial measurement of cell-mediated immunity was possible with the test, provided D.N.C.B. sensitivity was maintained by occasional skin patch tests.
Cell Migration Inhibition↗
Reactions to dinitrochlorobenzene in patients with neuroblastoma and survival.
To determine the relationship of cell-mediated immunity (CMI) to survival, I studied 67 children with the histologically confirmed diagnosis of neuroblastoma. CMI was measured by testing the ability of patients to develop sensitization to dinitrochlorobenzene (DNCB) and to respond to challenge. Reactions at the challenge sites were considered positive only when induration and swelling were present. Ninety percent of the patients with localized neuroblastoma and 27% of those with disseminated neuroblastoma were DNCB reactive. This suggested that patients with DNCB-positive reactions have a better chance of survival than those who are DNCB negative. Some patients with disseminated disease were evaluated in longitudinal studies, and alterations in reactivity did occur with changes in disease status and/or chemotherapy. The suggestion was made that this test systme is potentially useful in estimating survival in children with neuroblastoma.
Child↗
Effects of murine tumors on delayed hypersensitivity to dinitrochlorobenzene. I. Description of anergy caused by transplanted tumors.
In the murine model presented for tumor-associated immune suppression, normal BALB/c mice displayed significant foodpad swelling when sensitized on the flank with 2 mg dinitrochlorobenzene (DNCB) dissolved in dimethyl sulfoxide and challenged in a footpad with 0.05 mg DNCB 10 days later. This reaction in challenged footpads seemed to be a classic delayed hypersensitivity reaction, since it took 24 hours to develop and included an extensive mononuclear infiltrate. The reaction was transmissible from sensitized to normal mice by the transfer of lymphoid cells but not to serum. When sensitized 10 days after tumor inoculation, mice bearing either an allogeneic melanoma or a syngeneic lymphoma or fibrosarcoma did not demonstrate delayed hypersensitivity to DNCB.
Animals↗
Detection of human contact sensitivity to dinitrochlorobenzene by the migration inhibiton test.
The migration inhibitory factor (MIF) production of peripheral lymphocytes following exposure to dinitrophenylated microsomes derived from both human (DNP-hy-Mic) and guinea pig (DNP-gp-Mic) epidermis was quantitated to detect human contact sensitivity to dinitrochlorobenzene (DNCB). The lymphocytes from nonsensitized subjects did not generate MIF following exposure to either antigen. With DNP-gp-Mic as the antigen, MIF production was noted in only 1 out of 6 DNCB-sensitized subjects and was not significant statistically. With DNP-hu-Mic as the antigen, highly significant MIF production was observed in all 12 sensitized subjects ( p less than 0.0005). In order to confirm MIf production by sensitized lymphocytes following stimulation by DNP-hu-Mic, the subjects were actively sensitized with DNCB and MIF production was assessed before and after sensitization. Remarkable MIf production was noted in the lymphocyte cultures after sensitization, although no significant MIF production was observed before sensitization. MIF production of the sensitized lymphocytes cultured in the presense of DNP-hu-Mic generally correlated well with the results of patch testing, but not with the intensity of the skin test.
Animals↗