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Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.

Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course.

Animals↗

Collagen-induced arthritis in rats. Comparison of vitreous and cartilage-derived collagens.

An oil emulsion of purified type II collagen from bovine articular cartilage when injected intradermally into rats induced an inflammatory polyarthritis in 4 of 12 animals. When similarly injected, collagen purified from bonve vitreous induced arthritis in 6 of 12 animals. Studies of humoral and cell-mediated immunity to both collagen preparations demonstrated complete cross-reactivity. It is concluded that vitreous collagen shares the arthritogenic property of cartilage-derived type II collagen and that collagen from the two sources is indistinguishable in arthritogenic and immunologic properties.

Animals↗

Anisakis and eosinophil. I. Detection of a soluble factor selectively chemotactic for eosinophils in the extract from Anisakis larvae.

Studies were undertaken in order to determine if Anisakis larva itself has the ability to attract eosinophils. Extracts from Anisakis larvae were examined for both neutrophil and eosinophil chemotactic activities with both in vivo and in vitro assay systems. When the soluble extract was injected intradermally into normal guinea pigs, a profound accumulation of eosinophils was observed at the injection site. The cells started to accumulate at the site within 1 hr and the number of eosinophils at the site reached its peak at 8 hr after the injection of the extract. Such eosinophilic accumulation was enhanced in a dose-response fashion over the range of 0.5 to 50 micrograms protein. The strong chemotatic activity of the Anisakis extract for eosinophils was confirmed when in vitro chemotaxis assays were performed with Boyden chemotatic chambers. Interestingly, no chemotactic activity for neutrophils was found at those concentrations of the extract with which the eosinophil effect was observed. These results indicate that the factor described here, in addition to the various known immunologic factors, may play an important role in the development of eosinophilia in anisakiasis.

Animals↗

Non-efficacy of low-dose intradermal vaccination against hepatitis B in Down's syndrome.

Persons with Down's syndrome (DS) constitute a risk group for hepatitis B (HB) and are recommended to be immunized. Of 123 persons with DS in Orebro county screened for markers of HB, 31% had such markers; 16% were potentially contagious. 83 persons without markers participated in a comparative trial of the immunogenicity of a recombinant HB vaccine given either intramuscularly (IM) or in a lower dose intradermally (ID). Immunity developed in 73% after IM vaccination as compared to 29% of those given ID vaccination (p < 0.005). At 3-year follow-up half and two-thirds of the immune persons, respectively, had lost their immunity. Those > 30 years had a poor immunization response compared to the younger ones (p < 0.01). Only 19% of the non-responders developed immunity after an IM booster dose given 10 months after the third injection. Intradermal vaccination is not warranted in persons with DS, especially not in middle aged and older persons. A booster dose of vaccine does not ascertain immunity in those who do not respond with immunity to the ordinary immunization schedule. Post-vaccination immunity should therefore be controlled.

Adolescent↗

Human eotaxin induces alpha 4 and beta 2 integrin-dependent eosinophil accumulation in rat skin in vivo: delayed generation of eotaxin in response to IL-4.

The CC chemokine eotaxin, originally purified from bronchoalveolar lavage fluid of sensitized guinea pigs following allergen challenge, is a potent eosinophil-selective chemoattractant. In the present study, we have used (111)In-eosinophils and human eotaxin to characterize the profile of chemokine-induced eosinophil accumulation in vivo in rat skin. Intradermally injected eotaxin caused a dose-dependent accumulation of (111)In-eosinophils. Time course studies indicated that the response was rapid, since all the accumulation occurred within the first 1 to 2 h of eotaxin injection. The i.v. administration of anti-intercellular adhesion molecule-1, anti-vascular cell adhesion molecule-1, or anti-alpha4 integrin mAbs significantly inhibited the eosinophil accumulation induced by 100 pmol of human eotaxin by 73, 43, and 67%, respectively. Further, when (111)In-eosinophils were pretreated in vitro with anti-alpha4 integrin or anti-beta2 integrin mAbs, or with a combination of both mAbs, eotaxin-induced responses in vivo were reduced by 52, 49, and 68%, respectively. Eosinophil accumulation induced by intradermal IL-4, but not that induced by TNF-alpha or leukotriene B4, appeared to be mediated in part by endogenously generated eotaxin. Anti-eotaxin Abs significantly inhibited (54%) the later phases (24-28 h) but not the early phase (0-4 h) of the response to IL-4. This was consistent with eotaxin mRNA expression peaking at 18 h after IL-4 injection. Our findings show that human eotaxin is a potent inducer of eosinophil accumulation in vivo, this response being dependent on alpha4 integrin/vascular cell adhesion molecule-1 and beta2 integrin/intercellular adhesion molecule-1 adhesion pathways. Further, the eosinophil accumulation in response to IL-4 is partly mediated by endogenously generated eotaxin.

Animals↗

Cutaneous hypersensitivity reaction to injectable hyaluronic acid gel.

BACKGROUND: Injectable hyaluronic acid gel is a non-animal biomaterial used for soft tissue augmentation. OBJECTIVE: The dermal implantation of this naturally occurring polysaccharide is reported to be well tolerated by patients, with a longer duration in tissue than bovine collagen without any major local or systemic side effects. We report a case of an acute hypersensitivity reaction in a woman after her third injection for improvement of melolabial fold wrinkles. METHODS: An adverse granulomatous-like response to the intradermal injection of a modified hyaluronic acid gel is described. RESULTS: The patient developed indurated and erythematous papulocystic nodules in the melolabial folds bilaterally at the sites of injection. CONCLUSION: Injectable hyaluronic acid gel can be associated with severe allergic reactions and patients should be warned of this possible treatment side effect.

Acute Disease↗

Lymphatic clearance of the human skin in patients with acute deep vein thrombosis using a novel fluorescent technique.

The purpose of this study was to investigate lymphatic clearance of the human skin in patients with acute deep thrombosis of the femoral vein. In 13 patients with deep vein thrombosis and no other cause for swelling of the limbs, lymphatic clearance of the skin at the foot was measured. Ten microliters of fluorescein isothiocyanatedextran 150,000 were injected intradermally and the fluorescent light intensity of the deposit measured 10 min and 24 hours after injection by window densitometry. In addition, intralymphatic pressure was measured by the servo-nulling system. The results were compared with a sex- and age-matched control group. Fluorescent light intensity decreased by 23.8 +/- 12.3 arbitrary units or by a factor of 1.8 +/- 0.5 in patients with DVT after 24 hours, which was significantly less than in healthy controls (33.7 +/- 8.9 arbitrary units or by factor 5.0 +/- 4.1, p < 0.013). Intralymphatic pressure was not different between the two groups. These results indicate that lymphatic clearance is significantly reduced in the acute phase of deep venous thrombosis.

Adult↗

Treatment methods for extravasations of chemotherapeutic agents: a comparative study.

A rat model was used to compare early surgical intervention with injectable and topical antidotes with regard to their effectiveness in preventing cutaneous ulcers that were caused by intradermal injections of vesicant chemotherapeutic agents. The (animals) rats received bilateral flank injections of doxorubicin, vincristine, actinomycin D, mitomycin C, or carmustine (BCNU) in concentrations that were comparable to concentrations used for human patients; after the injections they underwent debridement at various intervals or received immediate applications of selected antidotes. Many "antidotes" which were frequently used, were not effective in limiting the size of the ulcer and in producing rapid healing of ulcers that were caused by experimental vesicant extravasations. Early surgical debridement was the most effective method of decreasing vesicant ulcer size and facilitating rapid ulcer healing of all the interventions tested.

Animals↗

[A randomized controlled study to compare bladder instillation therapy of anticancer agents and combination therapy with OK-432 injection in prevention of post-TUR recurrence of bladder cancer].

To evaluate the effects of bladder instillation chemotherapy of anticancer agents with OK-432 intradermal injection (group A) in preventing postoperative recurrence of bladder carcinoma, a randomized controlled study with intravesical instillation chemotherapy of anticancer agents (group B) as the reference standard was performed. As the anticancer agents, pepleomycin (PEP) was usually used at a concentration of 30 mg/30 ml physiological saline. OK-432 injection dose was gradually increased from 0.5 KE to 5.0 KE and maintenance dose was decided by local skin reactions. There were no differences in the patient's background factors between group A (22 cases) and group B (17 cases). The no-recurrence rate of bladder carcinoma was similar in the two groups, but the no-recurrence rate for the virgin tumor or the stage T0 cases was higher in group B. On the other hand, the values for the recurrent cases or the stage T1,2 cases was higher in group A. The SU-PS skin reaction as an immunological response was significantly higher in group A. There were no severe side effects derived from anticancer bladder instillation or OK-432 injection.

Administration, Intravesical↗

Intradermal rabies immunization for pre- and post-exposure prophylaxis.

Human diploid cell rabies vaccine and similar tissue culture-produced vaccines are too expensive for widespread use in India, but alternative regimes can reduce the cost of post-exposure treatment by 60%. Multiple-site intradermal injections of tissue culture vaccine have proved effective, economical and safe. As these vaccines are becoming more freely available, the intradermal method can now be used to accelerate the replacement of nervous tissue vaccines.

Culture Techniques↗

Wheal reactions in human skin after injection of leukotrienes B4, C4, D4 and E4.

Intradermal injections of 1-50 pmol leukotriene B4, C4, D4 and E4, (LTB4, LTC4, LTD4 and LTE4) were performed in healthy subjects and patients with recurrent urticaria. A wheal and erythema were seen 15 minutes after injection and were most marked after LTC4 and LTD4. LTE4 also produced a wheal whereas the reaction to LTB4 did not significantly differ from the saline control. When mixed with histamine no potentiation of the wheals was noted and no significant difference in reaction was observed between the healthy controls and those with urticaria.

Drug Hypersensitivity↗

Leukotriene B4-induced granulocyte trafficking in guinea pig dermis. Effect of second-generation leukotriene B4 receptor antagonists, SC-50605 and SC-51146.

Leukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated as a mediator in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB4 elicits a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4-dihydro-8-p ropyl-2H-1-benzopyran-2-carboxylic acid), a first-generation LTB4 receptor antagonist inhibited the chemotactic actions of LTB4 when coadministered into the dermal site and when given orally with ED50 values of 340 ng and 1.7 mg/kg, respectively. The second-generation LTB4 receptor antagonists SC-50605 (7-[3-[2(cyclopropylmethyl)-3-methoxy-4-(4-thiazolyl)phenoxy]propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid) and SC-51146 (7-[3-[2(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl] phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid) inhibited LTB4-induced chemotaxis when coadministered with ED50 values of 70 ng and 32 ng, respectively, and when given intragastrically with ED50 values of 0.10 and 0.09 mg/kg, respectively. SC-41930, SC-50605, and SC-51146 had oral durations of action of 5.5, 15, and 21 h, respectively. These potent, LTB4 receptor antagonists may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, where LTB4 is implicated as an inflammatory mediator.

Administration, Oral↗

Double-blind randomized efficacy field trial of alum precipitated autoclaved Leishmania major vaccine mixed with BCG against canine visceral leishmaniasis in Meshkin-Shahr district, I.R. Iran.

This study was designed to evaluate the efficacy of a single dose of aluminum hydroxide (alum) precipitated Leishmania major (Alum-ALM) vaccine plus BCG against canine visceral leishmaniasis. Three hundred and forty-seven healthy dogs with no anti-Leishmania antibodies were double-blind randomly injected intradermally with either 0.1ml of Alum-ALM (200 microg protein) mixed with BCG (182 dogs) or injected with 0.1ml of normal saline (165 dogs). The results of 16 months follow-up showed that the vaccine was safe and well-tolerated. Strong seroconversion using DAT and ELISA techniques at 16 months post-vaccination was considered as an indication of Leishmania infection. The incidence rate was 3.7% (6/162) in vaccinated group and 12.0% (17/141) in control group using DAT technique. The efficacy of the vaccine was calculated to be 69.3%.

Adjuvants, Immunologic↗

Effect of terbutaline, a beta 2-adrenergic receptor stimulating compound, on cutaneous reponses to histamine, allergen, compound 48/80, and trypsin.

The beta-adrenoceptor stimulating agent terbutaline (2 ng-2 microgram) injected intradermally in eight atopic subjects produced a dose-dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 microgram terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min. The flare response induced by histamine, the histamine liberator compound 48/80 and the proteolytic enzyme trypsin was not inhibited by terbutaline in the doses used, suggesting a selective action of terbutaline on the allergen-induced response. The weal response elicited by histamine and compound 48/80 was slightly reduced by 2 microgram terbutaline. It is suggested that pretreatment of the skin with terbutaline interferes with the ability of the cutaneous mast cells to respond to challenge with allergen and that terbutaline produces this effect in doses lower than those needed to counteract the permeability increasing effect of released mediator substances.

Adolescent↗

Radioautography of noradrenaline-14-C in atopic dermatitis.

Since storage-time of administered noradrenaline in the skin of patients with atopic dermatitis may be prolonged, it would be of interest to demonstrate the site of uptake of noradrenaline-(14)C in atopic dermatitis as compared with other eczematous and normal skins. Two adult patients with longstanding atopic dermatitis, a patient with contact dermatitis to nickel and one with normal skin, were studied. Identical sites in the four patients were injected intradermally with 0.02 mug. DL-noradrenaline-7-(14)C acetate. An 8-mm. punch biopsy of the injected site was performed 24 hours later. Radioautographs were developed between three and 199 days, according to the technique of Kopriwa and Leblond.(2) At 199 days, the number of grains in atopic dermatitic skin was greater than in contact dermatitis or normal skin. There was a concentration of grains over arrectores pilorum muscles and the upper one-third of the epidermis of atopic skin. Grains were also visible in proximity to arteriolar walls. There were few grains visible in the control sections. The results confirm earlier studies suggesting that atopic dermatitic skin retains noradrenaline longer than other dermatoses. Noradrenaline concentrates in the arrectores pilorum muscles and the upper epidermis. These findings may explain the cutis anserina (goose-flesh) appearance in atopic dermatitis.

Adult↗

The role of epinephrine in the reactions produced by the endotoxins of gram-negative bacteria. I. Hemorrhagic necrosis produced by epinephrine in the skin of endotoxin-treated rabbits.

Extensive lesions of dermal hemorrhagic necrosis occurred in rabbits when epinephrine (or norepinephrine) was injected into the skin within 4 hours after an intravenous injection of endotoxin. As little as 5 microg. of intradermal epinephrine, and 1 microg. of intravenous endotoxin, were sufficient to produce lesions. Similar lesions, but smaller in size and surrounded by a zone of acute inflammation, were produced by intradermal injection of a mixture of comparable amounts of endotoxin and epinephrine. No lesions were produced by combinations of endotoxin with serotonin, pitressin, or ephedrine. Both types of epinephrine-endotoxin lesion were prevented by pretreatment with cortisone, dibenzyline, and chlorpromazine. They were not prevented by heparin or nitrogen mustard. The lesions produced by intradermal mixtures of epinephrine and endotoxin were greatly enhanced in size and severity in animals treated with nitrogen mustard. Both types of lesion were prevented in rabbits rendered "tolerant" by repeated injections of sublethal amounts of endotoxin. It is concluded that endotoxin has the property of altering the reactivity of blood vessels to epinephrine in such a way that this hormone becomes a potent necrotizing agent. The possibility that this effect may represent a basic mechanism in the various intoxicating actions of endotoxin, and certain implications of this hypothesis, are discussed.

Animals↗

Localization of the sentinel node in breast cancer: identical results with same-day and day-before isotope injection.

BACKGROUND: Although the technique of sentinel lymph node (SLN) biopsy in breast cancer is not fully standardized, an increasing number of centers map the SLN by using radioisotope supplemented by blue dye, and most have injected isotope on the day of surgery. Here we directly compare the results of same-day and day-before isotope injection in a large series of breast cancer patients having SLN biopsy with our mature technique. METHODS: Starting with our 961st SLN procedure for breast cancer, 1320 consecutive patients had SLN biopsy after the injection of unfiltered 99mTc-labeled sulfur colloid given as a single-site, low-volume (0.05 ml) intradermal injection: 933 on the day of surgery (1-day protocol) and 387 on the day before (2-day protocol). All had intraparenchymal injection of blue dye. RESULTS: The two groups were comparable in age, tumor location, histopathologic characteristics, and number of SLNs identified. LSG taken at 2 hours in the 2-day protocol was positive more often than LSG performed at 30 minutes in the 1-day protocol, and nonaxillary sites of lymphatic drainage were seen in <1% of each group. Absolute isotope counts and the ratio of SLN to axillary background counts were similar. Isotope localization of the SLN succeeded in a comparable fraction of patients, as did SLN identification overall. CONCLUSIONS: The results of SLN mapping with same-day and day-before injection of radioisotope are virtually identical. The logistical advantages of day-before injection do not compromise the success of the procedure.

Adult↗

IL-11 protects human microvascular endothelium from alloinjury in vivo by induction of survivin expression.

IL-11 can reduce tissue injury in animal models of inflammation but the mechanism(s) is unknown. When C.B-17 SCID/beige mice bearing human skin grafts are injected i.p. with human PBMC allogeneic to the donor skin, infiltrating T cells destroy human microvessels by day 21. Intradermal injection of human IL-11 (500 ng/day) delays the time course of graft microvessel loss without reducing the extent of T cell infiltration. Protective actions of IL-11 are most pronounced on day 15. IL-11 has no effect on T cell activation marker, effector molecule, cytokine expression, or endothelial ICAM-1 expression. IL-11 up-regulates the expression of survivin, a cytoprotective protein, in graft keratinocytes and endothelial cells. Topical application of survivin antisense oligonucleotide down-regulates survivin expression in both cell types and largely abrogates the protective effect of IL-11. We conclude that in this human transplant model, IL-11 exerts a cytoprotective rather than anti-inflammatory or immunomodulatory effect mediated through induction of survivin.

Adjuvants, Immunologic↗