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PubMed1993

Sodium cromoglycate: evidence of tachykinin antagonist activity in the human skin.

The mechanism of action of the antiasthmatic drug sodium cromoglycate (SCG) is unclear. One possibility is that SCG antagonizes the effects of the tachykinin substance P (SP), an agent known to cause airway edema. However, when SP is inhaled by humans, it has no demonstrable effect on airway function; therefore, the possibility that SCG prevents SP-induced changes in microvascular permeability was examined in human skin in vivo where potent edema-producing effects are seen. SCG (5-500 nmol) caused significant (P < 0.05) dose-dependent inhibition of SP-induced edema (wheal) formation when coadministered by intradermal injection. There was no effect on the nonreceptor-mediated flare response. SCG also significantly (P < 0.05) inhibited the wheal response to the related tachykinin neurokinin B but had no inhibitory effect on the cutaneous responses to histamine and prostaglandin E2. In addition, SCG (0.1-10 mM) caused dose-dependent inhibition of binding of SP labeled with 125I-labeled Bolton-Hunter to a number of tissues known to contain SP binding sites, as assessed by autoradiography. These concentrations were equivalent to the final concentrations of SCG found to inhibit the wheal response in the skin. The possibility that SCG interacted with SP was investigated both by gel filtration and high-performance liquid chromatography. No strong interaction was demonstrated with an 8,000 M excess of SCG under both hydrophobic and hydrophilic conditions. These results raise the possibility that SCG may have tachykinin antagonist properties.

Adult↗
PubMed2000

Mediation of the immunomodulatory effect of beta-estradiol on inflammatory responses by inhibition of recruitment and activation of inflammatory cells and their gene expression of TNF-alpha and IFN-gamma.

BACKGROUND: Estrogen has long been reported to show immunomodulatory effects on immune responses, yet, its specific anti-inflammatory mechanism is not clear. METHODS: In this study, we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on both T cell-independent and T cell-dependent inflammations, and the associated immune mechanism, in female mice. The T cell-independent inflammation was locally induced either with an intradermal injection of olive oil in the footpad, or by an intraperitoneal injection of proteose peptone (PP). The T cell-dependent inflammation was induced by an intraperitoneal injection of the purified protein derivatives (PPD). RESULTS: While E2 inhibited olive oil-induced inflammation as monitored by the decrease in footpad swelling, it did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by cells at the inflammatory locus. E2 also inhibited PP-induced inflammation as monitored by the decrease in the number of inflammatory peritoneal exudate cells (PEC) coinciding with a marked decrease in the number of macrophages and granulocytes (Gr. 1+). While E2 did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by PP-elicited PEC, it decreased both gene expression and production of TNF-alpha. E2 also decreased the number of cells expressing the lymphocyte function-activated protein-1 in PP-elicited PEC, but not for CD62L. In purified protein derivative-induced T cell-dependent inflammation, E2 decreased the total cellularity of PEC and the relative numbers of CD3+ and CD4+ T cells, and the number of cells expressing the lymphocyte activation markers CD40, CD44, CD69 and IL-2Ralpha in PEC. Furthermore, while E2 did not affect the gene expression of the early T lymphocyte activation protein-1 by PEC, it decreased the gene expression of INF-gamma. CONCLUSION: Collectively, the results suggest that E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.

Adjuvants, Immunologic↗
PubMed2006

A cutaneous allergen neutralisation test that correlates with the duration of venom immunotherapy.

BACKGROUND: Despite the well-documented efficacy of Hymenoptera specific immunotherapy (SIT), there is no safe method to reliably characterise the patient level of protection. Only poor correlations between protection and allergen-specific serum immunoglobulins have been found, and a sting challenge is the only means to evaluate the efficacy of immunotherapy. Therefore, we aimed to develop a cutaneous test that measures in vivo neutralisation of the Hymenoptera venom. MATERIALS AND METHODS: Twenty-four patients with wasp venom allergy were included in the study. Wasp-specific serum IgE, IgG and IgG4 were measured by ImmunoCAP. Dilutions of the individual patient sera were intradermally injected into the forearm. Then, wasp venom extract was injected into these sites to quantitatively assess the formation of wheals and flares. RESULTS: The results show that during the course of SIT, patient sera gained the capacity to neutralise skin reactions to wasp venom extracts in vivo. The test correlated with the duration of SIT as well as with the concentration of IgG and IgG4. CONCLUSION: The in vivo neutralisation test may become a promising tool in allergy diagnostics as well as in monitoring the success of SIT in patients undergoing allergen SIT.

Adult↗
PubMed1989

Influence of aging on the histamine release and membrane fluidity of rat peritoneal mast cells.

The maturational changes in the degree of homologous passive cutaneous anaphylaxis (PCA) and the histamine release from peritoneal mast cells induced by several secretagogues were studied using Wistar rats (4-40 weeks old). Although the increase in vascular permeability of the rat skin induced by intradermal injection of histamine did not change significantly from one maturation period to the next, 6- to 8-weeks old rats were both the most susceptible to PCA reactions and the most responsive to histamine-releasing stimuli. Among rats in this age group (6-8 weeks), the fluidity of the resting cell membrane and the extent of membrane fluidity increase in response to compound 48/80 were greatest. Analysis of the lipid composition of mast cells indicated that the ratio of cholesterol to phospholipids was lowest at the age of 6-8 weeks. From the present study, we concluded that the maturational changes in the extent of histamine release seem to be related to membrane fluidity, which has a profile similar to that of maturation.

Aging↗
PubMed1988

Human recombinant interleukin-1 alpha is proinflammatory in normal human skin.

The proinflammatory effects of recombinant human interleukin-1 alpha (HRIL-1 alpha) have been determined in the skin of normal human volunteers. Intradermal injection of 10, 50 and 100 U HRIL-1 alpha produced dose-related erythema which first appeared at 2 h, was maximal around 24 h, persisted for up to 48 h, and was associated with oedema. Histological examination revealed dermal mononuclear cell infiltrates, which were accompanied by neutrophils at 4 and 8 h. Injection of heat-treated HRIL-1 alpha (100 U) produced no erythema or oedema. These results demonstrate the potent proinflammatory properties of HRIL-1 alpha in human skin.

Adult↗
PubMed1992

Effect of substance P and Sar9Met(O2)11-substance P on cutaneous capillary permeability in guinea pig skin.

The purpose of this study was to assess the effect of several drugs on the increase in cutaneous capillary permeability induced by intradermal injection of substance P (SP) and Sar9Met(O2)11-SP in guinea pig skin. On the one hand, the increase in cutaneous capillary permeability was partly reduced by spantide, promethazine, atropine or SR 40037, an inhibitor of the angiotensin-converting enzyme. On the other hand, norepinephrine and B3824, a B2-antagonist of bradykinin, showed an enhancing effect. Our results suggest that the effect of SP and Sar9Met(O2)11-SP in guinea pigs is partly mediated by histamine and acetylcholine, and that there is a relationship between tachykinins and bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Effect of locally administered heparins on delayed-type hypersensitivity reactions.

Inflammatory reactions involved in delayed-type hypersensitivity (DTH) are associated with extravascular coagulation and fibrin deposition. Heparin and other anticoagulants administered systemically inhibit DTH reactions but the direct effect of intradermally injected heparin on the development of DTH skin responses has not been reported. The effects of heparin on the DTH reaction elicited by ovalbumin (OVA) in guinea pigs 1-3 weeks after sensitization were examined. Unfractionated heparin, low affinity heparin (LAH; non-anticoagulant) and high affinity heparin (HAH; anticoagulant) were injected together with suboptimal amounts of OVA. Heparin and LAH enhanced skin induration, LAH (0.5 micrograms) by an average of 50% above that due to OVA alone at 24 h (p less than 0.01). In contrast, HAH (0.5 micrograms) significantly reduced skin induration at 24 h. Heparin and LAH also significantly increased cellular infiltration with LAH having the greater effect. At 4 h the infiltrate consisted mainly of neutrophils whereas at 24 h mononuclear cells predominated. Fibrin deposition, assessed both by immunohistology and quantitation of radioactive fibrin extracted from skin test sites, was increased by 30% when OVA was tested in the presence of LAH. Mast cell heparin released locally at sites of DTH has the potential to modulate these reactions in either a pro- or anti-inflammatory manner. This study is the first to demonstrate differences in the capacities of LAH and HAH to modulate cell-mediated inflammation.

Animals↗
PubMed1991

Plasmapheresis in solar urticaria.

Three patients with solar urticaria were treated with plasmapheresis. By intradermal injection of in vitro irradiated serum the existence of a circulating photoallergen was demonstrated in cases 1 and 2 but not in case 3. Plasmapheresis induced complete remission of solar urticaria in case 1 and transient improvement in case 2. In case 3, however, no beneficial effect was observed. It is suggested that some patients with solar urticaria, probably those with a circulating photoallergen, may benefit from plasmapheresis.

Adult↗
PubMed1986

Necrobiosis lipoidica: clinical and immunofluorescent study.

Fourteen patients with necrobiosis lipoidica (NL) were carefully evaluated clinically and histologically. Ten of these patients (71%) had diabetes and most of them were treated with insulin (8 of 10 patients). Trauma was found as an immediate triggering factor in 6 patients (43%) and a possible preceding factor in 3 more cases. No immunoglobulins were found in the lesional skin of NL. Intradermal injections of histamine in healthy skin of legs led to deposition of immunoglobulins and complement (C3) in skin blood vessel walls in 4 of 12 patients studied (30%). These results suggest that immune complexes might be involved only in few cases of NL. Preceding trauma combined with metabolic and inflammatory changes could be an important triggering factor in the etiology of NL.

Adolescent↗
PubMed1977

Intradermal triamcinolone treatment of psoriatic onychodystrophy.

Intradermal injections of triamcinolone acetonide have used in the treatment of psoriatic onychodystrophies in seven patients. The therapeutic response initially is good but relapses appear inevitable. One patient developed rather persistent periungual hypopigmentation, thereby limiting the routine recommendation of this form of treatment.

Adolescent↗
PubMed1994

Increased airways responsiveness in mice depends on local challenge with antigen.

In Balb/C mice, painting the skin with ovalbumin (OVA) over a period of 14 days resulted in sensitization of the animals. This was documented by the appearance of OVA-specific IgE and IgG1 antibodies and increased total serum IgE levels. In addition, in regional (inguinal) lymph nodes of sensitized animals, OVA-specific T cell proliferative responses and increased IgE and IgG production could be detected in vitro. Sensitized animals also developed immediate cutaneous responses to intradermal injection of OVA. In contrast to previous results following OVA sensitization via the airways, increased airways responsiveness to electrical field stimulation (AREFS) of tracheal smooth muscle preparations was not observed in skin-sensitized mice. Only 24 h after a single local challenge of the airways with aerosolized OVA on Day 14 could a significant increase in AREFS be observed in skin-sensitized but not nonsensitized control mice. These data indicate that sensitization of Balb/C mice to OVA via the skin provides an effective means for inducing a systemic IgE and IgG1 antibody response and immediate cutaneous hypersensitivity. Despite these IgE and IgG1-mediated responses, however, the development of altered function as reflected in an increase in AREFS was dependent on challenge with the allergen via the airways.

Administration, Cutaneous↗
PubMed1970

A method for the calculation of the relative contributions of recruitment and enhancement to human eccrine sweating.

The rate of eccrine sweating has been studied by collecting samples in unventilated capsules from human subjects following subdermal or intradermal injections of acetyl-beta-methylcholine and under moderate total body heat exposure. The rate of sweating in a given area of skin could increase by recruitment of fresh glands, enhanced output of the already active glands, or some combination of both.A theoretical analysis shows how recruitment and enhancement can be calculated separately, assuming the existence of a maximal rate of sodium reabsorption by eccrine sweat glands, a sodium concentration of 145 muEq/ml in the precursor fluid, the absence of significant water reabsorption, and the absence of back-diffusion of sodium. The results indicate that, depending on the experimental conditions, an increased rate of sweating can be attributed mainly to recruitment, to enhancement, or to a combination of both.

Absorption↗
PubMed1985

Accumulation of leukotriene C4 and histamine in human allergic skin reactions.

To determine whether lipoxygenase products of arachidonic acid metabolism are released in vivo during human allergic cutaneous reactions, we serially assayed chamber fluid placed over denuded skin sites for the presence of both C-6 peptide leukotrienes (e.g., LTC4, LTD4, and LTE4) and leukotriene B4 (LTB4), using radioimmune assay and HPLC separation, and compared it to histamine (assayed radioenzymatically) in 13 atopic and two nonatopic volunteers. Skin chamber sites challenged with ragweed or grass pollen antigen (250-750 protein nitrogen units/ml) for the first hour and phosphate-buffered saline (PBS) for the next 3 h were assayed hourly and compared to sites challenged with PBS alone. As assessed by HPLC, LTC4 composed greater than 85% of the C-6 peptide leukotriene released at any skin site, whereas little LTD4 or LTE4 was detected. LTC4 was present in significantly greater concentrations at antigen sites as compared to PBS-challenged sites throughout the 4-h period. Minimal concentrations of LTB4 were found throughout this time period and were not different at antigen or PBS sites. Histamine was present in significantly greater concentrations at antigen rather than PBS sites, but the pattern of release was different from that of LTC4. Peak histamine release invariably occurred during the first hour and decreased progressively thereafter, whereas the greatest amounts of LTC4 were detected during the 2nd to 4th hours. The amount of LTC4 accumulating at the site was dependent upon the dosage of antigen used in the epicutaneous challenge. We have demonstrated in this study that of the leukotrienes assessed LTC4 is released in the greatest quantity in situ during in vivo allergic cutaneous reactions and that it is present at such sites for at least 4 h after antigen challenge. Since intradermal injection of LTC4 in humans induces wheal and flare responses that persist for hours, our findings support the hypothesis that LTC4 is an important mediator of human allergic skin reactions.

Chromatography, High Pressure Liquid↗
PubMed1988

Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin.

Angiotropin is a differentiation factor for microvascular endothelial cells isolated from serum-free cultures of lectin-activated, porcine monocytes. We used an ear lobe model in rabbits, single intradermal injection of angiotropin to induce phenotypical changes of the endothelial cells in capillaries and postcapillary venules, vascular engorgement, and subsequent angiogenesis in dose-dependent manner. The vascular changes are associated with epidermal and stromal cell proliferation. Angiogenesis and tissue proliferation occur in the absence of tissue necrosis and do not lead to scar formation. Angiotropin-induced angiogenesis is not inhibited by local dexamethasone although it involves a defined turnover of inflammatory cells. Proliferation is transient and regressive events follow. The overall tissue reaction resembles changes found in the undamaged skin margin of a primary healing wound during the inflammatory/proliferative phase. From these observations we conclude that angiotropin is an important secretory product of activated peripheral macrophages that triggers inflammatory and proliferative reactions in wound healing by activating microvascular endothelial cells.

Angiogenesis Inducing Agents↗
PubMed1998

Effects of angiogenic growth factors and a penetrance enhancer on composite grafts.

Skin-cartilage composite grafts are invaluable tissues used in facial reconstruction, yet their survival is unpredictable beyond a 1-cm diameter. In this study, the angiogenic growth factors basic fibroblast growth factor (bFGF) and endothelial cell growth factor (ECGF) and a penetrance enhancer (dimethyl sulfoxide [DMSO]) were applied to composite grafts to determine their effects on survival and vascularization. We applied ECGF, bFGF, and DMSO either topically or by intradermal injection to 120 auricular composite grafts (3.0 cm diameter) in New Zealand White rabbits. Dermabrasion was performed in 2 groups to attempt to increase transdermal delivery. Graft viability and vascularity were evaluated 3 weeks later by template analysis and angiography. In the results, ECGF and bFGF, when grouped together, had a 40% increase in vascular ingrowth as compared to controls (p < .001). However, neither ECGF nor bFGF increased graft survival. A coincidental finding was that DMSO with dermabrasion significantly improved graft viability (>100%) with or without an angiogenic agent (p < .02). The potential of DMSO with dermabrasion to increase composite graft viability warrants further investigation.

Administration, Topical↗
PubMed1986

Comparative cutaneous histamine release by neuromuscular blocking agents.

Normal values of cutaneous wheal diameter following intradermal injection of six neuromuscular blocking drugs were determined. The relative cutaneous histamine-releasing ability of each drug was derived from calculated dose-response relationships. Equipotent neuromuscular blocking doses were found to have a cutaneous histamine releasing ability relative to pancuronium (= 1) of vecuronium 1.1: suxamethonium 1.7; alcuronium 5; atracurium 52; d-tubocurarine 172. A significant (P less than 0.001) variation was found between the dose-response slopes perhaps suggesting a variation in the mechanism of histamine release.

Alcuronium↗
PubMed2000

Elevated oxidative stress in skin of B6C3F1 mice affects dermal exposure to metal working fluid.

Metal working fluids (MWFs) are widely used in industry for metal cutting, drilling, shaping, lubricating, and milling. Potential for dermal exposure to MWFs exists for a large number of men and women via aerosols and splashing during the machining operations. It has been reported earlier that occupational exposure to MWFs causes allergic and irritant contact dermatitis. Previously, we showed that dermal exposure of female and male B6C3F1 mice to 5% MWFs for 3 months resulted in accumulation of mast cells and elevation of histamine in the skin. Topical exposure to MWF also resulted in elevated oxidative stress in the liver of both sexes and the testes in males. The goal of this study was to evaluate the interaction between oxidative stress in the skin and topical application of MWF. Oxidative stress in skin ofB6C3F1 mice of both sexes was generated by intradermal injection ofthe hydrogen peroxide (H2O2) -producing enzyme, glucose oxidase with polyethylene glycol (GOD+PEG). In mice given GOD+PEG, topical treatment with MWF (200 microl, 30%, for 1, 3, or 7 days) resulted in a mixed inflammatory cell response, accumulation of peroxidative products, and reduction of GSH content in the skin. Such changes were not observed with MWF treatment alone. These data indicate that oxidative stress can enhance dermal inflammation caused by occupational exposure to MWF.

Administration, Cutaneous↗
PubMed1995

Sudomotor function in human poikilothermia.

Hypohidrosis predisposes to hyperthermia and may indicate generalized thermoregulatory failure. To assess the sweating capacity in human poikilothermia, we performed a quantitative analysis of the central and peripheral sudomotor pathways in four women with acquired poikilothermia (aged 29 to 38 years) and nine controls. Heat challenge in a climatic chamber (ambient temperature 40 degrees C, 50% relative humidity) for 180 minutes revealed that both sweat secretion and evaporative weight loss were significantly lower in the patients than in the controls (p < 0.01). Temperature thresholds for thermal sweating were markedly elevated in at least two patients, whereas a third patient showed no sweating response. Stimulation of the eccrine sweat glands by intradermally injected acetylcholine during reduced core temperature (34.9 +/- 0.7 degrees C) revealed a significantly reduced sweating response in all patients (p < 0.01); the sudomotor response to pilocarpine iontophoresis was reduced or absent in three patients. We conclude that the generalized thermoregulatory sudomotor failure in these patients was attributable primarily to disorders of the central sudomotor drive; the impaired postganglionic sudomotor response is temperature related and possibly secondary to (long-standing) poikilothermia. Quantification of heat-dissipating capacity is pivotal for diagnosing severe thermolability and may help to prevent serious heat illness.

Acetylcholine↗