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PubMedDate not supplied

Cellular and molecular mechanisms in the induction phase of contact sensitivity.

During the induction phase of contact sensitivity, hapten-specific Th1 cells are primed by epidermal Langerhans cells. These Langerhans cells present hapten on MHC class II molecules and provide costimulatory signals. This presentation discusses the induction of cytokines in Langerhans cells and keratinocytes by haptens and their regulatory effects on contact sensitivity. Haptens were painted on the skin of normal BALB/c mice and epidermal cells were prepared at various times thereafter. Langerhans cell-derived interleukin (IL)-1 beta mRNA was observed as early as 15 min after hapten paining. In keratinocytes, tumor necrosis factor-alpha, IL-1 alpha, IP-10, MIP-2 and IL-10 were found to be up-regulated. IL-1 beta appeared to be a 'master' cytokine since it was able to mimic the effects of haptens, such as the increase of MHC class II expression in Langerhans cells and activation of the cytokine cascade. Injection of anti-IL-1 beta monoclonal antibody prior to hapten application completely prevented epicutaneous sensitization. In vivo application of IL-10 by intradermal injection prior to epicutaneous application of TNCB induced antigen-specific tolerance and impeded the induction of proinflammatory cytokines.

Animals↗
PubMed1976

Effects of subcutaneously administered adrenaline on human eccrine sweating, with special reference to the physiological significance of the adrenergic sweating mechanism.

The effects of a small dose (3-6 mug/kg) of subcutaneously administered adrenaline on thermal sweating were studied while subjects were at rest and during or after excerise by means of continuous monitoring by resistance hygrometry of the sweat rate in the forearm area. In most cases, the sweat rate either decreased or did not change significantly following the adrenaline injection, however, among athletic subjects it showed a mild increase in a few cases, mostly during or after exercise. In the area receiving the intradermal injection of an alpha-adrenergic blocking agent, tolazoline, phentolamine or dihydroergotoxine, subcutaneous adrenaline consistently caused an increase in sweat rate. Adrenaline (15 mug) was injected intravenously with similar results. Noradrenaline was used in place of adrenaline in some cases, and the results were essentially the same as, but less distinct than, those with adrenaline. The results indicate that a small dose of subcutaneous adrenaline has dual effects, with the sweat-inhibitory effect generally predominating over the sweat-facilitatory one, with occasional exceptions in association with exercise and/or physical training. The former effect is largely secondary to its vasconstrictive effect, whereas the latter appears to be secondary to its systemic effects, such as central and calorigenic ones. It is concluded that adrenaline within a physiological range exerts no direct action on human eccrine sweat glands.

Adrenergic alpha-Antagonists↗
PubMed1978

Protective immunity and possible autoimmune regulation in amebiasis.

Hamsters were injected intradermally with axenic trophozoites of a pathogenic strain of Entamoeba histolytica, and controls similarly with culture medium. Localized lesions were produced in all animals injected with amebae. After the lesions healed all the animals were challenged intrahepatically with axenic amebae. Extensive liver abscesses were produced in all the controls, but a small abscess in only one of the vaccinated hamsters. In the protected animals the indirect hemagglutination antibody titers were high (I:512), while in the controls they ranged between 1:32 and 1:128. In the vaccinated hamster with the small abscess the IHA titer was 1:32. To investigate a possibility of autoimmune regulation in amebiasis, sera of hamsters with experimental amebic liver abscesses were acidified and tested by counter-current-immunoeletrophoresis against untreated autologous sera and amebic antigen. In most cases there was a direct correlation between the two titers. With human antisera in autologous systems there was reactivity against anti-amebic IgG antibodies. These experiments showed that autoimmune complexes may be present in cases of hepatic amebiasis. As in chronic hepatitis and some malignancies, it is possible that immune complexes have an immunoregulatory function in amebiasis.

Animals↗
PubMed1989

The chemotactic properties of cartilage glycosaminoglycans for polymorphonuclear neutrophils.

Cartilage breakdown products have been tested for their effects on the locomotion of rat polymorphonuclear neutrophils in vitro. Chondroitin sulphate, keratan sulphate and hyaluronic acid were used in checkerboard migration assays to differentiate chemotaxis from chemokinesis. All test substances showed both chemokinetic and chemotactic activities. The same substances were then injected intradermally to determine their effects on vascular permeability and leukocyte accumulation in vivo. There was no significant effect on vascular permeability 30 minutes after injection as measured by a dye-leakage method. Histological examination of skin sections taken 6 hours after injection showed modest accumulations of polymorphonuclear neutrophils. It is suggested that cartilage breakdown products may account for the persistence of polymorphonuclear neutrophils in some chronic inflammatory joint diseases.

Animals↗
PubMed1985

Lymphscintigraphy in peripheral lymphedema using technetium-labelled human serum albumin: normal and abnormal patterns.

Lymphscintigraphy using Tc-99m human serum albumin (HSA) was examined in 23 patients with peripheral leg lymphedema. Each was injected intradermally with one mCi in the medial web space bilaterally. Images of the lower pelvis and both thighs were obtained within five minutes after injection using an extralarge field view camera GE 500A with low energy all purpose collimator interfaced with G.E. Star computer. These images were acquired in dynamic byte mode, 128 X 128 matrix size, every minute for 40 minutes. Delayed images for this region and of both legs were also taken at 90 minutes and time activity curves from comparable regions of interest over the inguinal area bilaterally were generated. Three patterns emerged: 1--normal lymph flow (12 patients) characterized by symmetrical or nearly symmetrical early appearance of lymphatics (medial bands) with visualization of inguinal and pelvic lymph nodes in both early and delayed images. Time activity curves showed step ladder rise, in "pulses" every three to four minutes. 2--enhanced lymph flow pattern (6 patients) was characterized by rapid movement of radiolabelled albumin through dilated lymphatics, occasionally with subcutaneous pooling, and both larger and more numerous inguinal and pelvic nodes on the lymphedematous side. 3--obstructed lymph flow (5 patients) was characterized by subcutaneous pooling, absent lymphatics, (medial bands) and flat, time activity curve on the lymphedematous side (only background activity) and absent inguinal and pelvic nodes. On delayed images, where lymphatic obstruction was incomplete there was delayed appearance of inguinal pelvic nodes which were fewer and smaller compared to the nonedematous side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

[Histologic manifestations in the skin in alpha-lactoalbumin intradermal tests in patients with chronic urticaria].

Intradermal injection with alpha-lactoalbumine, 2000 PNU/ml was carried out in seven patients (1 male, 6 females, mean age 32.4 years) suffering from milk intolerance. None of the patients had a positive allergen-specific IgE antibodies in the sera (RAST). Skin test was performed on the volar part of the forearms at the same time. The area of skin reaction was estimated and measured within 36 hours on the right arm. Skin biopsy was done with a 4 mm punch after 8 hours from site of antigen injection on the left arm. Various cells infiltrating the site of antigen instillation were present. Leukocytoclastic vasculitis was only found in patients with dual intradermal reaction (immediate and late onset of response; 8 12 hours). These results indicate that local skin reaction to alpha-lactoal-bumine is mediated by diverse immune mechanisms, and that it may be of clinical significance for the diagnosis of cow milk allergy in adults.

Adult↗
PubMed1995

Inhibition of the induction of delayed-type and contact hypersensitivity by calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP)-containing nerves are frequently associated anatomically with epidermal Langerhans cells (LC), and LC Ag-presenting function is down-regulated by CGRP. To investigate possible regulation of cutaneous immunity by CGRP, we examined its effect on the induction of delayed-type hypersensitivity (DTH) and contact hypersensitivity (CHS). A system of immunity to the murine spindle cell tumor S1509a (H-2a) was employed to examine induction of DTH by LC. This system requires exposure of epidermal cells (EC) to GM-CSF for induction of substantial immunity. EC were prepared from CAF1 mice (H-2a/d) and Thy-1+ cells deleted. EC were exposed for 16 h to GM-CSF with or without CGRP. EC were then pulsed with tumor-associated Ags (TAA), washed, and injected s.c. into mice three times at 7-day intervals for immunization. Mice were challenged for a DTH response by injection of a hind footpad with TAA-pulsed EC, and 24-h footpad swelling assessed. Exposure of EC to CGRP significantly inhibited induction of DTH. To examine the effect of CGRP administered in vivo on induction of immunity, 530 pmol of CGRP or diluent alone was injected intradermally into the dorsum of the left ear of naive mice 8 h and 3 h before epicutaneous application of a hapten at the injected site. Mice were challenged on the right ear 7 days later and 24 h ear swelling was assessed. CGRP significantly inhibited the induction of CHS whereas calcitonin had no effect. Furthermore, when hapten was applied at a site distant from CGRP administration, no inhibition of CHS was observed, suggesting that the effect of CGRP is local. These data support the concept that CGRP may be an endogenous regulator of immune function and also suggest the possibility that CGRP or its analogues administered in vivo might have therapeutic utility as immunomodulators.

Animals↗
PubMed1996

Effects of MTX and BN52021 on PAF-induced chemotaxis of PMNs and intraepidermal accumulation of inflammatory cells in guinea pigs.

OBJECTIVE: To investigate the effects of methotrexate (MTX) and platelet activating factor (PAF) antagonist ginkgolide B (BN52021) on PAF induced chemotaxis of neutrophils. MATERIALS AND METHODS: All guinea pigs were randomly divided into 12 groups. They were given different dosages of MTX and BN52021 by intra-abdominal injections. The random and chemotactic migration of polymorphonuclear leukocytes (PMNs) were measured by the agarose method. The backs of all guinea pigs were given intradermal injections of PAF and the numbers of the infiltration of inflammatory cells into the skin were determined. RESULTS: MTX inhibited random migration and chemotactic migration of PMNs to PAF, LTB4 and PAF-induced intraepidermal accumulation of inflammatory cells in dose- and time-dependent fashion. BN52021 specially inhibited PAF-induced chemotaxis of PMNs and intraepidermal accumulation of inflammatory cells, but did not inhibit PMNs random migration and LTB4-induced chemotaxis of PMNs. CONCLUSIONS: The inhibition of PMNs activities may be part of the mechanism of MTX therapy for psoriasis; BN52021 is a selective inhibitor of PAF-induced chemotaxis of PMNs, and therefore can be useful in the treatment of some inflammatory dermatoses such as psoriasis.

Animals↗
PubMed1984

Efficacy of streptococcal preparation OK-432 for gastric cancer patients--comparison between intradermal and intramuscular injection.

Nonspecific immunotherapy with OK-432, penicillin and heat treated lyophilized powder of Su-strain of streptococcus pyogens A3, was evaluated in patients with recurrent or unresectable stomach cancer to assess the relative benefit of the preparation administered by different routes. Comparative studies were made of the variation in immunological parameters, the survival rate and the incidence of adverse reactions in two groups of patients with uniform background factors: 24 receiving the preparation intradermally and 18 receiving intramuscular doses of the preparation. In for former group, no serious adverse reaction occurred but more marked improvement was achieved in various immunological parameters examined. The survival rate was significantly higher (P = 0.005) for patients receiving intradermal than those receiving intramuscular doses of the preparation. The results of the present study showed that the preparation is of greater value when it is administered intradermally than intramuscularly.

Adult↗
PubMed2001

Pharmacodynamics induced by direct electric current for the treatment of 5-fluorouracil resistant tumor: an animal experiment.

The repeated use of chemotherapy to treat patients with colorectal carcinoma may be limited by the fact it creates resistance cells. However, we have observed a remarkable decrease in certain types of drug resistance in patients treated with direct electric current. Experimental studies were therefore performed in animals to determine the differences in pharmacodynamics between chemotherapy with and that without electric treatment. Tumors were created in BALB/c mice by intradermal injection of 0.25 ml 4 x 10(6) Colon 26 cells/ml in the abdomen. Seven days later the mice were divided into two groups: controls and those that underwent electric treatment. Direct electric current (1,000 V, 0.2-0.8 microA) was passed between a platinum electrode inserted intradermally and the earth during and for 1 h after a single intravenous injection of 5-fluorouracil (5-FU; 12.5 mg ml(-1) kg(-1)). Peripheral blood samples were collected before and 5, 10, 20, 30, 45, and 60 min after the injection of 5-FU. Concentrations of 5-FU in the sera and tissues were measured by HPLC. The intratumoral concentrations of 5-FU in the electric treatment group were higher than those in the controls (P<0.05, two-factor analysis of variance), but the serum concentrations were not statistically different between the two groups. Pharmacodynamic changes were thus observed as a result of electrostatic treatment during chemotherapy. This elevated 5-FU concentration in the tumor tissue is considered one of the reasons for the effective inhibition of 5-FU resistance in clinical cases.

Animals↗
PubMed1990

Immune response of mallard ducks treated with immunosuppressive agents: antibody response to erythrocytes and in vivo response to phytohemagglutinin-P.

The ability of two in vivo tests to assay immune competence of mallard ducks (Anas platyrhynchos) treated with various immunomodulatory agents was examined. Skin responses to phytohemagglutinin-P (PHA-P) injected intradermally and serum antibody levels produced in response to sheep red blood cells (SRBC) were measured. As measured by the skin response to PHA-P, ducks injected intramuscularly with cyclophosphamide or cyclosporine did not respond differently from control-injected ducks. Dexamethasone injected intramuscularly significantly suppressed the skin response to PHA-P. As measured by antibody levels in response to SRBC, ducks injected intramuscularly with cyclophosphamide responded with antibody titers similar to controls. Cyclosporine injected intramuscularly reduced the level of immunoglobulin (Ig) G significantly in one of two experiments. Dexamethasone injected intramuscularly reduced peak total and IgG titers. These experiments provide information on the viability of these two in vivo tests to reflect immune competence of mallard ducks.

Animals↗
PubMed1995

Suppression of human melanoma cell growth and metastasis by the melanoma-associated antigen CD63 (ME491).

CD63 has been identified in human melanoma cells by a number of different monoclonal antibodies (MAbs). Studies with MAbs have shown that expression is most marked in naevi and early forms of cutaneous melanoma and reduced in vertical growth phase and metastatic lesions. To investigate further the role of CD63 in progression of melanoma, genomic CD63 was transfected into a CD63-negative human melanoma cell line using an episomal vector. The stable transfected melanoma cells had similar growth rates to control transfected melanoma cells in vitro but much lower growth rates when injected intradermally into athymic nude mice. The CD63-transfected cells also had a reduced number of metastases in the peritoneal cavity and subcutaneous sites when injected intravenously. MAb against CD63 did not influence the growth of CD63-transfected melanoma cells in vitro. Our results confirm previous studies using H-ras-transformed NIH3T3 fibroblasts and suggest that CD63 may have a role as a tumor suppressor gene in human melanoma that acts to limit invasion and progression of melanoma.

Animals↗
PubMed2003

Intramuscular injection of antigens and adjuvant preferentially decreases 18:2n-6 and 18:3n-3 in pig neck muscle.

Linoleic (18:2n-6) and alpha-linolenic acids (18:3n-3) have many important physiological functions including immunomodulation. We tested how immunization influences the metabolism of 18:2n-6 and 18:3n-3 in the neck muscle of pigs. At 35 d old, pigs received either an intramuscular neck injection containing hen egg white lysozyme (HEWL), killed Mycobacterium tuberculosis, and Freund's complete adjuvant (immunized) or PBS (control). At 49 d old, immunized pigs received a booster injection of HEWL and Freund's incomplete adjuvant, and the control pigs received PBS into the neck. At 56 d old, all pigs received an intradermal injection of Mycobacterium bovis into the hind leg to induce a delayed-type hypersensitivity (DTH) reaction. At 57 d old, immunized pigs had a twofold increase in serum haptoglobin, a 10-fold increase in antibodies to HEWL, and the skinfold at the DTH reaction site was 10 times thicker than the controls. Both 18:2n-6 and 18:3n-3 (% composition) were approximately 25% lower in muscle TG, 40% lower in FFA, 50% lower in phospholipids, but not different in cholesteryl esters of the neck muscle of immunized pigs. The antigens in this model induce an increased response in the innate (haptoglobin), humoral (antibodies), and cellular (DTH) immune systems as well as a preferential decrease of 18:2n-6 and 18:3n-3 in the inflamed neck muscle. It appears that 18:2n-6 and 18:3n-3 are preferentially metabolized (possibly beta-oxidized) in response to antigens.

Animals↗
PubMed2001

Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism.

Regulation of innate immunity may be an effective means of cancer control. Delaying cancer onset is regarded as an important mode of action in cancer prevention. We have been investigating the chemopreventive mechanisms of Lactobacillus casei Shirota (LcS), a probiotic strain. In this study, we evaluated the effect of LcS on tumor onset and the involvement of natural killer (NK) cells using a 3-methylcholanthrene-induced carcinogenesis model. C3H/HeN mice were divided into three groups, according to treatment: vehicle-treated, treated with vehicle only; control, 3-methylcholanthrene treated; LcS, 3-methylcholanthrene and LcS treated. 3-Methylcholanthrene was injected intradermally at 7 weeks of age. LcS was mixed into the diet (0.05%, w/w), which the mice were fed from the day of 3-methylcholanthrene injection onward. Tumor incidence was observed weekly. Profiles of splenic NK cells, in vitro cytotoxicity and the proportion, in the early stage of carcinogenesis were analyzed at 5 weeks after the injection. The tumor suppressive effect of LcS was also evaluated in a beige mouse model that is genetically deficient in NK cells. LcS delayed tumor onset and reduced tumor incidence in the results with C3H/HeN mice (P< 0.05). More specifically, tumor incidence in the control group was 33% at 6 weeks after the injection and 83% at 11 weeks as opposed to 0 and 42%, respectively, in the LcS group. NK cell cytotoxicity was significantly higher than in the control group, and the number of NK cells also increased in the LcS group of C3H/HeN mice. However, LcS failed to suppress tumorigenesis in the beige mouse. These findings suggest that enhancement of the cytotoxicity of NK cells by LcS delays tumor onset.

Animals↗
PubMed1997

Peripherally administrated morphine attenuates capsaicin-induced mechanical hypersensitivity in humans.

We examined the hypothesis that peripheral morphine can modulate pain and hyperalgesia/allodynia in the human capsaicin model. Subcutaneous injections of 1 mL morphine (1 mg/mL) in one arm and of 1 mL 0.9% saline in the other arm were made prior to bilateral intradermal injections of 50 microL (6 mg/mL) capsaicin. All injections were made on the volar aspect of the arm. Before and after the capsaicin injections, spontaneous pain and pain evoked by repetitive von Frey filament stimulation was rated on a numerical rating scale; furthermore, pressure pain thresholds were determined. The area in which von Frey filament stimulation evoked pain and the area of visible flare were mapped after the capsaicin injection. Capsaicin injection resulted in spontaneous pain on the saline-injected side not significantly different from that on the morphine-injected side. However, capsaicin injections gave rise to significantly less pain evoked by mechanical stimuli, as well as to a significantly smaller area of mechanical hypersensitivity, on the morphine-injected side compared with the saline-injected side. These results suggest that morphine can modulate sensitization mechanisms involved in the development of capsaicin-induced mechanical hypersensitivity.

Adult↗
PubMed1992

Comparison of skin changes induced on mice by either group A type 12 or group G streptococci.

Adult Swiss webster mice were injected with 3 x 10(6) colony-forming units (cfu) of group G or 2.5 x 10(6) cfu of group A streptococci at intradermal injection sites on the right and left paralumbar areas of the back. The mice were sacrificed at intervals between 4 hours and 14 days post-injection (p.i.) and full thickness biopsies of skin 10 mm in diameter encompassing the sites of injection were taken. One tissue specimen was homogenized in PBS and plated to determine the number of cfu, while another was used for histopathological studies. The number of viable group A and group G streptococci in the tissue increased to 3 x 10(9) cfu by 96 hours p.i.: after 192 hours p.i. the group A cells had declined to 2.7 x 10(6) cfu compared to 1.1 x 10(8) cfu for group G cells. No streptococci of either group were detected at 336 hours (14 days p.i.). Gross edematous lesions induced by either streptococcus group were evident on all animals at 24 hours (p.i.). Group G streptococci lesions were larger and persisted longer than lesions induced by group A. Histological examination consistently revealed more inflammation and necrosis in tissue sections from mice injected with group G streptococci.

Animals↗
PubMed1980

Searches among mycobacterial cultures for antileprosy vaccines.

All mycobacteria species share some antigens, so there may be cultivable mycobacterial cultures that can provide vaccine protection against leprosy. Vaccine protection against Mycobacterium leprae infections in mice has been demonstrated for M. leprae itself, as living or heat-killed suspensions, and for Mycobacterium bovis (BCG), as living suspensions. Results are reported here with 17 other cultures. The mycobacterial suspensions were injected intradermally, and the mice were challenged in the footpad with infectious suspensions of M. leprae. In two experiments the mice were also challenged by footpad injections of 10(7) heat-killed M. leprae so the footpad enlargment could be measured. That some mycobacterial suspensions were immunogenic for some of their own antigens was suggested by reactions at the vaccine site and enlargement of the regional lymph nodes. Some mycobacterial suspensions also stimulated footpad enlargement on challenge by homologous suspensions or by challenge with M. leprae suspensions. Consistent protection against infectious challenge with M. leprae was observed only with BCG and M. leprae, however.

Animals↗
PubMed1978

[A new method for assaying anti-inflammatory drugs. Quantitative analysis of pigment leakage into skin by Chromatoscanner CS-900 (author's transl)].

Although the pigment leakage method is one of the most conventional for determining vascular permeability, accuracy in macroscopic measurement of the diameter of the stained area with an arbitary scale leaves much to be desired. We developed a simple and beneficial method for quantitative assay using a densitometer (Chromatoscanner CS-900). Guinea pigs weighing 300 approximately 350 g were used. Formalin as a phlogistic, in a dose of 2.3 approximately 37 mg was injected intradermally in the shaved skin of the back, and 15 mg/kg of pontamine blue was then given into the femoral vein. One hour after the injection the animals were sacrificed and the skin of the back, which was stained by the leaked pigment, was stripped off and allowed to adhere to a wooden plate for 24 hours. Reflection and a zig-zag scanning technique were used to measure the volume of the leaked pigment. There was a liner relationship between the dose of formalin and the integrated values. A dose-dependent relationship was also obtained when histamine, serotonin, kallikrein and bradykinin were used as phlogistics. Representative anti-inflammatory drugs such as aspirin, hydrocortisone, oxyphenbutazone, benzydamine, diclofenac sodium, sodium salicylate and aminopyrine depressed the leakage due to formalin. Depression of leakage by aspirin in a dose of 400 mg/kg was the most remarkable. Pigment leakage elicited by histamine, serotonin, kallikrein and bradykinin was examined on the same individual animal. Aspirin more than the other agents depressed the leakages due to bradykinin and kallikrein. Hydrocortisone and oxyphenbutazone depressed the leakage due to bradykinin, serotonin and histamine, but enhanced that due to kallikrein. The results obtained were consistent with those of a previous study and as this method is simple and more reliable, it is applicable for assay of anti-inflammatory compounds.

Animals↗