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PubMed1993

Vitiliginous vs pigmented skin response to intradermal administration of interferon gamma.

BACKGROUND AND DESIGN: Decreased sensitization and elicitation of contact allergens in vitiliginous skin has been described. This may be related to altered epidermal Langerhans cell migration with bound hapten to dermis and draining lymph nodes. The aim of the present study was to detect the potential ability of vitiliginous skin to respond to an in vivo immunologic stimulus such as intradermal injections of interferon gamma (IFN-gamma). Vitiliginous and normal pigmented skin of each patient was injected intradermally with 10 micrograms of recombinant IFN-gamma diluted in 0.1 mL of sterile water for 3 consecutive days. On day 5, punch biopsy specimens were obtained from the injected sites. Histologic and immunohistochemical staining was performed on all sections. The cryostat sections were stained with adenosine triphosphatase as well as with the indirect immunoperoxidase technique employing murine monoclonal antibodies to HLA-DR, ICAM-1, CD1, CD11a, and CD18. RESULTS: HLA-DR and ICAM-1 expression by epidermal cells, combined with perivascular accumulation of mononuclear cells with CD11a and CD18 expression, was observed in all sites injected with IFN-gamma. However, absence of an effect on the epidermal Langerhans cell population was noted only on the vitiliginous skin. CONCLUSION: The reactivity of depigmented and pigmented skin was found to be different after IFN-gamma administration, with fewer CD1-positive cells in the depigmented skin. As adenosine triphosphatase staining also showed fewer positive cells, it may be concluded that no effect on the migration of epidermal Langerhans cells was noted in the involved skin. This may shed light on the immunologic aberration seen in vitiliginous skin.

Adenosine Triphosphatases↗
PubMed2004

Enhancement of both cellular and humoral responses to genetic immunization by co-administration of an antigen-expressing plasmid and a plasmid encoding the pro-apoptotic protein Bax.

BACKGROUND: Transfecting cells with plasmid DNA encoding the protein Bax causes programmed cell death (apoptosis) and results in the formation of cell fragments (apoptotic bodies). It has been known for some time that when dendritic cells phagocytose apoptotic bodies derived from tumor cells, an immune response to tumor antigens can be generated. METHODS: Gene expression in the skin was evaluated after intradermal injection with plasmids encoding fluorescent proteins. Plasmids encoding foreign antigens were co-injected intradermally with Bax-encoding plasmids or control plasmids to elicit both humoral and cytotoxic immunity. Immune responses to the antigens were assessed by ELISA and cytotoxicity assays. RESULTS: We demonstrate here that injection of a mixture of reporter gene plasmids into the skin results in the expression of both plasmids in the large majority of the transfected cells. It is known that immune responses to multiple antigens can be elicited by co-injection of separate individual plasmids. When mice were injected with equal quantities of two antigenic plasmids and either the Bax plasmid or a noncoding control plasmid, antibody responses were increased 4-8-fold in the Bax group. Similarly, cytotoxic T lymphocyte (CTL) responses in the Bax group showed an 80% increase in the number of lytic units per million cells. CONCLUSIONS: This data shows that simply including the apoptosis-inducing Bax plasmid along with antigen-expressing plasmids may provide a significant enhancement of immune responses to DNA vaccines. Published in 2004 by John Wiley & Sons, Ltd.

Animals↗
PubMed1996

Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens.

Peptide epitopes derived from differentiation antigens of the melanocyte lineage have been identified in human melanomas and normal cultured melanocytes as targets for MHC-restricted cytotoxic T lymphocytes (CTL). Characterization of multiple CTL-defined antigenic determinants and the presence of corresponding precursor CTL open perspectives for the development of antigen-based vaccines. In the present study, we determined the CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase and gp100/Pmel17 in 10 HLA-A2+ melanoma patients and 10 healthy individuals. Then, we examined the immunological effects and toxicity of intradermal inoculation of synthetic melanoma-associated peptides. Six patients with advanced melanoma received weekly intradermal injections of 6 melanoma-associated peptides and the influenza matrix peptide as a control for 4 consecutive weeks. DTH reactions were observed in 5/6 patients at the injections sites of the tyrosinase signal peptide and of the influenza matrix peptide. No toxic side effects were observed. Changes in CTL reactivity after peptide vaccination were assessed by an MLPC assay for each peptide. Generation of peptide-specific CTL was documented against Melan A/MART-1-derived peptide epitopes, the tyrosinase signal peptide and the influenza matrix peptide after vaccination. A decreasing CTL response against the internal tyrosinase peptide was documented in 1 patient through the course of vaccination and a decrease in DTH reactions. No major tumor regressions were observed. Two patients with rapidly progressive disease before vaccination have shown disease stabilization since vaccinations started. In conclusion, our results demonstrate that peptide alone injected intradermally may generate antigen-specific DTH reactions and an increase of antigen-specific CTL reactivity.

Adult↗
PubMed1971

Cutaneous reactions to intradermal prostaglandins.

1. The effects of intradermally injected prostaglandins (PGs) E(1), E(2), F(1alpha) and F(2alpha) have been examined in the rat and in man.2. PGE(1) and PGE(2) caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, bradykinin, and 5-hydroxytryptamine), but PGF(1alpha) and PGF(2alpha) were only slightly active even at a dose of 1 mug.3. Prior administration of mepyramine and methysergide, or depletion of skin mast cell amines with compound 48/80, indicated that PGE(2) exerted its permeability effect in the rat by a release of mast cell amines.4. Nanogramme doses of PGE(1) and PGE(2) or microgramme doses of PGF(1alpha) and PGF(2alpha) injected intradermally into the human forearm induced weal and flare responses.5. It is concluded that prostaglandins E(1) and E(2) can act as intermediates in the production of hyperaemia and oedema resulting from cell damage in the rat and man.

Amines↗
PubMed2002

Experimental itch in sodium lauryl sulphate-inflamed and normal skin in humans: a randomized, double-blind, placebo-controlled study of histamine and other inducers of itch.

BACKGROUND: Investigations of pruritogenic substances in humans have involved intradermal injections in normal skin; itching of inflamed skin has been little studied. OBJECTIVES: To develop an itch model with provocation of itch in experimentally inflamed skin as well as in normal skin, using subjects as self-controls. METHODS: In 32 non-atopic volunteers aged 21-30 years, the skin of five selected test sites on one volar forearm was pretreated for 24 h with large Finn chambers containing 1% sodium lauryl sulphate (SLS) used as a standard contact irritant to induce inflammation. Twenty microlitres of different pruritogenic substances [histamine, substance P, neurokinin A, neurokinin B, trypsin, platelet-activating factor (PAF) and serotonin] and saline as control were injected intradermally into the inflamed test sites and in corresponding non-treated sites on the opposite forearm. The test individuals scored itch intensity on a visual analogue scale for 20 min, and weal area was then measured. : RESULTS: Histamine and substance P induced itch in both normal and inflamed skin compared with a saline reference. Neurokinin A, trypsin, PAF and serotonin only elicited itch in normal skin, and neurokinin B neither elicited itch in normal skin nor in inflamed skin. Itch was induced in normal and SLS-inflamed skin to a similar magnitude. However, weal area after histamine was significantly (P < 0.001) larger in inflamed skin when compared with normal skin. CONCLUSIONS: Histamine and substance P elicited itch to the same degree in normal skin and inflamed skin pretreated with SLS despite a stronger weal response in inflamed skin. Mediators present in inflamed skin did not potentiate itch, a c-fibre-mediated neuronal response. The weal reaction is based on enhanced vascular permeability (protein extravasation). A greater skin perfusion in inflamed skin may therefore have increased the weal size. We propose an experimental model in humans for testing of itch involving both normal and inflamed skin. The model has the potential for use in evaluating new topical and systemic treatments of itch.

Adult↗
PubMed1965

INDUCED UNRESPONSIVENESS TO SIMPLE ALLERGENIC CHEMICALS. II. INDEPENDENCE OF DELAYED-TYPE HYPERSENSITIVITY AND FORMATION OF CIRCULATING ANTIBODY.

Normal guinea pigs fed chemical haptens develop a specific state of unresponsiveness, inhibiting subsequent development of dermal sensitization with the same hapten and modifying profoundly the synthesis of anaphylactic antibody in response to hapten conjugated to guinea pig proteins. The degree of unresponsiveness has been tested by exposing hapten-fed animals to intense haptenic stimulation. Animals of groups that were demonstrably unresponsive to picryl chloride could be made to form hapten-specific antibody by injecting picrylated bovine gamma globulin. Specific anaphylactic-type antibodies, presumably 7S gamma(1), were synthesized, and in animals given PBGG adsorbed to alumina there arose a measurable concentration of precipitating antibody, presumably 7S gamma(2), perhaps slightly earlier than in similarly treated control animals. Attempts to impose contact-type reactivity on such unresponsive animals met with limited success. Injection of picrylated guinea pig erythrocyte stromata in a complete Freund's adjuvant, with subsequent applications of picryl chloride to the dermis, led to definite contact sensitivity to 0.3 per cent picryl chloride, whereas parallel treatment of normal control animals induced sensitivity to 0.006 or 0.002 per cent. By this double method of stimulation, hapten-fed animals did not advance in sensitivity by reason of the secondary dermal applications of the simple chemical, whereas control animals developed increasingly higher sensitivity by these contacts in what appeared to be a stepwise manner. Picryl chloride-fed guinea pigs injected intradermally with picryl chloride either after or before forming picryl-specific circulating antibody still remained unable to develop picryl-specific contact hypersensitivity. Control animals synthesizing picryl-specific antibody subsequently responded to intradermal injection of picryl chloride with contact-type sensitivity. Interpretations of these results are discussed and the view is presented that delayed-type hypersensitivity and circulating antibodies of the varieties measured here are formed independently of each other.

Allergens↗
PubMed1981

An attempt to use vincristine and colcemid to measure proliferative rates in normal human epidermis in vivo.

A range of doses of vincristine (0.5-10 micrograms) or colcemid (5-100 micrograms) injected intradermally into normal volunteers failed to yield any significant accumulation of arrested mitoses. This was despite an apparently successful block of cells in metaphase by the highest three doses of each drug. Possible reasons for the failure to see accumulation are discussed. The results suggest that normal human epidermis is not a suitable system for application of the metaphase-arrest technique using intradermal injection.

Adult↗
PubMed1985

Inflammatory oedema induced by synergism between calcitonin gene-related peptide (CGRP) and mediators of increased vascular permeability.

The potent vasodilator calcitonin gene-related peptide (CGRP, human synthetic), when mixed with histamine and injected intradermally in the rabbit, induced a marked potentiation of local oedema. CGRP also potentiated oedema induced by other mediators of increased microvascular permeability in the rabbit; bradykinin, platelet-activating factor (Paf), C5a des Arg, N-formylmethionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). Substance P alone, or mixtures of substance P and CGRP, failed to induce oedema in rabbit skin. In rat skin, however, substance P induced oedema and this was potentiated by CGRP. CGRP had a protracted potentiating action following intradermal injection in the rabbit. The time for half loss of activity for CGRP was 40.1 +/- 7.5 min compared to 18 +/- 1 min for prostaglandin E2 (PGE2). No loss of potentiating activity was detected after incubation of CGRP in rabbit plasma or blood for 60 min. We postulate that endogenous CGRP, if released locally from nerve endings, could have a marked enhancing effect on oedema induced by other mediators in an inflammatory reaction.

Animals↗
PubMed1991

A calcitonin gene-related peptide (CGRP) antagonist (CGRP8-37) inhibits microvascular responses induced by CGRP and capsaicin in skin.

1. The effect of the calcitonin gene-related peptide (CGRP) antagonist CGRP8-37 on responses to CGRP and other mediators was investigated in rabbit dorsal skin. 2. Blood flow changes at intradermally-injected sites were measured by a multiple site 133xenon clearance technique. CGRP8-37 had little effect on blood flow at doses up to 0.3 nmol/site, when injected alone, although a significant increase in blood flow was observed at the highest dose tested (1 nmol/site). 3. CGRP8-37 dose-dependently inhibited the increased blood flow induced by human alpha CGRP and human beta CGRP, but had no effect on equivalent vasodilator responses induced by vasoactive intestinal peptide (VIP) and prostaglandin E1 (PGE1). CGRP8-37 showed a preferential ability to inhibit alpha CGRP (IC50 0.04 nmol), when compared with beta CGRP (IC50 greater than or equal to 0.3 nmol). 4. Capsaicin, which selectively activates sensory nerves, caused a dose-dependent increase in blood flow when injected intradermally into rabbit skin. The effects of capsaicin (0.01-0.1 mumol/site) were inhibited by CGRP8-37 (0.3 nmol/site), with a partial but significant attenuation of blood flow induced by the highest dose of capsaicin. 5. Oedema formation, induced by intradermal histamine injection (3 nmol/site), was measured in rabbit skin by the local accumulation of intravenously-injected 125I-labelled albumin. Vasodilator doses of CGRP, PGE1 and capsaicin potentiated, in a synergistic manner, oedema formation induced by histamine. GRP8-37 totally inhibited the potentiating effect of CGRP, partially inhibited the synergistic effect of capsaicin, but did not affect PGE1-induced responses.6. The results suggest that capsaicin acts to release a rabbit form of CGRP in skin and that CGRP8 37 is a useful antagonist for investigating the potential of CGRP as a neurogenic mediator of inflammation.

Alprostadil↗
PubMed1988

Absence of specific histologic changes in guinea pig skin treated with bullous pemphigoid antibodies.

Previous studies have reported that intradermal injections of bullous pemphigoid antibodies into guinea pigs can reproduce the histologic and immunohistologic features of bullous pemphigoid lesions. In this study we examined this model to determine its reproducibility and suitability for testing other types of anti-BMZ antibodies. Twenty guinea pigs were injected intradermally with 0.1, 0.3, or 0.5 ml of either bullous pemphigoid serum or IgG fraction containing high-titer complement-binding anti-BMZ antibodies or an equivalent volume of normal human serum or IgG fraction as control. Sites were biopsied at intervals after injection and were examined by routine histology and direct immunofluorescence. The results showed (a) no difference in the incidence of dermal epidermal separation or type of inflammation in experimental and control sites; (b) no evidence of an eosinophil-rich inflammatory reaction typical of bullous pemphigoid; (c) an absence of linear BMZ deposits of IgG and complement in the majority of sites injected with bullous pemphigoid antibodies; and (d) no correlation between dermal-epidermal separation and deposition of immune reactants at the BMZ. These results suggest the histologic changes seen in guinea pigs that are administered intradermal injections of bullous pemphigoid antibodies are nonspecific and that the model is not suitable for testing the pathogenicity of anti-BMZ antibodies in sera or IgG fractions.

Animals↗
PubMed1996

Persistent cutaneous pseudolymphoma after intradermal gold injection.

After intradermal testing with goldsodiumthiomalate (GSTM), 5 out of 8 patients developed skin papules at the test sites, which persisted up to 20 months. The lesions were surgically excised. Histology revealed pseudolymphoma of B and T cell type containing follicular structures and occasional small granulomas. The amount of histiocytic cells among B and T lymphocytes was pronounced, including acid cysteine proteinase inhibitor (ACPI) positive follicular dendritic cells, CD68 positive macrophages, factor XIIIa positive dermal dendrocytes and S-100 positive cells. By electron microscopy, the macrophages contained endosomes loaded with crystalloid material which contained gold in X-ray microanalysis. Atomic absorption spectrophotometry also confirmed the presence of gold in one specimen. Thus GSTM seemed to accumulate in tissue macrophages leading to constant immunologic activation with lymphoid proliferation and histiocytic response.

Adolescent↗
PubMed1999

Putative salivary allergens of the cat flea, Ctenocephalides felis felis.

The cat flea, Ctenocephalides felis felis, is the major initiator of flea bite hypersensitivity in dogs. Previous analyses of whole extracts of the flea and flea salivary secretions have failed to identify the allergens responsible. We dissected >2000 salivary glands from adult female fleas, extracted them into buffered saline containing protease inhibitors and fractionated the extract using gel permeation HPLC. Dogs were classified as hypersensitive to fleas (flea-feeding positive, FF+) or insensitive (flea-feeding negative, FF-) using a provocative test with live fleas. The allergenicity of the components of the salivary gland extract was tested by intradermal injection of samples of the column eluates. Dogs were also injected intradermally with a sample of whole salivary gland extract, and with histamine as a positive control. Negative control injections consisted of eluate from the column collected prior to fractions containing any protein. The skin of FF- dogs either did not respond or had a minimal response (a bleb approximately 2 mm larger than the injection blebs at the negative control injection sites) to all fractions and to the whole extract; histamine control injections produced positive responses (defined as wheals 5 mm greater than the blebs at the negative control injection sites) in all dogs. The skin of three of the nine FF+ dogs reacted positively to injection of a fraction containing protein/s with apparent MW 40k. Five other FF+ dogs reacted positively to the fractions containing proteins with apparent MW 12-8k. A single dog responded with very large, red wheals to injection of both the approximately MW 40k and MW12-8k fractions. These findings suggest that proteins with apparent MW 40k and MW 12k-8k are important in flea bite hypersensitivity. This work also supports a previous finding that mice which had been exposed to flea bites had antibodies to proteins with approximately MW 40k that were detected in salivary secretions of the flea.

Allergens↗
PubMed2003

Late asthmatic reactions induced by inhalation of allergen-derived T cell peptides.

In individuals with atopy and asthma, allergen-derived T cell peptides injected intradermally induce isolated late asthmatic reactions (LARs) followed by bronchial hyporesponsiveness to peptide, inhibition of the allergen-induced cutaneous late-phase reaction, and altered T cell function in vitro. Laboratory animal data indicate that "activation" and "tolerance" also occur if peptides are inhaled. In this study, we show that inhalation of Fel d 1-derived peptides induced isolated LAR in individuals with asthma sensitive to cat allergen comparable with that previously demonstrated using intradermal injection. LARs were accompanied by eosinophilia and nonsignificant elevations of total cysteinyl leukotrienes in the sputum. Unlike the intradermal route, repeated inhalation of peptides was not associated with abrogation of the LAR and produced a sputum eosinophilia comparable with the first exposure. In addition, there was no inhibition of the cutaneous late-phase reaction to whole cat dander. Thus, isolated LAR induced by inhaled, allergen-derived peptides represent a novel model of provoked asthma and are not associated with the induction of hyporesponsiveness ("tolerance") in the skin or lung.

Administration, Inhalation↗
PubMed1994

Lpr and MRL background gene involvement in the control of adjuvant enhanced arthritis in MRL-lpr mice.

The MRL-lpr mouse strain develops a mild spontaneous arthritis which can be enhanced by the intradermal injection of complete Freund's adjuvant (CFA). In this study we examined the requirement of the lpr gene and background MRL genes on CFA-enhanced murine arthritis. MRL+, MRL-lpr, AKR/J, and B6-lpr mice (experimental) and B6 mice (control) were injected intradermally with CFA containing M. tuberculosis H37 RA. The development of swelling and erythema was monitored for 1 month after the injection, when the histopathology of the joints was investigated. It was found that while 74% of both 7-month-old MRL + and 3-month-old MRL-lpr mice and 11% of AKR/J mice displayed clinically visible arthritis, B6, B6-lpr, and 3-month-old MRL+ did not develop the condition after CFA treatment. In accordance with the clinical observations, the histopathological changes were manifested only in older MRL+, AKR/J and 3-month-old MRL-lpr mice. One month after the CFA injection, milder changes were observed in the MRL+ than in the MRL-lpr mice, with the MRL+ mice developing a disease of similar severity to uninjected MRL-lpr mice. The AKR/J mice demonstrated the least severe histopathological changes. In the long term (150 days) more severe destructive changes could be demonstrated in the cartilage and bone of the MRL+ mice although the average histological scores did not show statistically significant differences from those found in the MRL+ 30 days after injection. The serological evaluation of the adjuvant-injected mice demonstrated significantly enhanced antibody production to type II collagen and M. tuberculosis, but did not correlate with the disease activity. These observations suggest that while the lpr gene causes a more severe early effect, background genes other than the lpr are more involved in the adjuvant-enhanced arthritis-afflicted mice.

Age Factors↗
PubMed1999

Inhibitory effect of heparin on skin reactivity to autologous serum in chronic idiopathic urticaria.

BACKGROUND: Most patients with chronic idiopathic urticaria (CIU) show cutaneous reactivity to intradermal injection of autologous serum. In some cases this reactivity is associated with the presence of autoantibodies directed against IgE or IgE receptors expressed on mast cells, whereas in others no autoimmune mechanisms can be documented. OBJECTIVES: The aims of this study were to compare the cutaneous reactivity to serum and plasma samples in a series of patients with active CIU and to address the mechanisms of the inhibitory effect exerted by heparin on the cutaneous responsiveness to the histamine-releasing factors (HRFs) present in CIU serum. METHODS: Fourteen patients with CIU were injected intradermally with autologous serum, plasma (anticoagulated by either heparin or EDTA), or serum samples to which heparin had been added. The effects of heparin injection on cutaneous responsiveness to allergens was tested in 5 atopic patients. Moreover, in a set of experiments sera were also adsorbed with Sepharose-conjugated heparin. RESULTS: All the patients had positive cutaneous reactions to autologous serum injection. When heparinized plasma was injected, negative reactions were observed in 12 of 14 patients, and a sizable reduction in the wheal-and-flare reactions was recorded in the remaining 2. Compared with results obtained with serum, no substantial change was observed in 6 of 8 patients injected with EDTA-anticoagulated plasma. When heparin was added to serum, abrogation of skin reactivity was seen; nonetheless, no change in the cutaneous response to allergens was associated with locally administered heparin in 5 atopic patients with no history of CIU. Finally, adsorption of CIU sera with solid-phase heparin abrogated the ability to induce cutaneous reactions in 5 of 7 patients, whereas in the remaining 2 a sizable reduction was observed. CONCLUSIONS: These data indicate that heparin is able to profoundly inhibit the cutaneous response to HRFs present in the sera of patients with CIU. Although the precise level of action of this heparin-mediated effect is unclear from present data, preliminary evidence seems to indicate that heparin could directly interfere with HRFs present in CIU sera.

Antibodies, Anti-Idiotypic↗
PubMed1981

Antigenic, adjuvant and permeability enhancing properties of melittin in mice.

Melittin, a mast cell lytic agent which comprises 50% of the protein content of bee venom, may be responsible for some of the severe reactions produced by bee stings in allergic and non-allergic individuals. We therefore investigated some of the biologic properties of this molecule in mice and found that repeated intradermal injections of melittin without adjuvant induced IgE formation in mice. In addition, melittin as well as another surfactant, saponin, were potent adjuvants for IgE formation in mice when mixed with ovalbumin (Ov). Titres of 1280 and 2560 to ovalbumin were produced in CBA mice after two injections of melittin and Ov or saponin and Ov. Melittin was also shown to have an enhancing effect on the vascular permeability induced by an antigen antibody interaction in mouse skin. Evan's blue dye was injected intravenously into ovalbumin-sensitized mice which had been injected intradermally with ovalbumin alone, melittin alone or a mixture of melittin and ovalbumin. The amount of local extravasation of dye was significantly greater in the area injected with the melittin and ovalbumin mixture than the amount of dye obtained from the skin site injected with melittin alone plus that extracted from the site injected with ovalbumin alone.

Adjuvants, Immunologic↗
PubMedDate not supplied

Tumor necrosis factor-alpha and ultraviolet B light have similar effects on contact hypersensitivity in mice.

Acute, low dose ultraviolet B (UVB) radiation impairs the induction of dinitrofluorobenzene (DNFB)-specific contact hypersensitivity (CH) in some, but not all, inbred strains of mice. Although C3H/HeN mice are UVB-susceptible by these criteria, the closely related strain, C3H/HeJ proved to be UVB-resistant. Since the only known important genetic difference between these strains is a polymorphism at the Lps locus which governs sensitivity to bacterial lipopolysaccharide (LPS), we examined the possibility that UVB radiation achieves its immune effects via an action directly or indirectly related to LPS. We found that intradermal injections of LPS failed to impair the induction of CH when DNFB was painted at the skin injection site. However, tumor necrosis factor-alpha (TNF alpha), a cytokine released from LPS-sensitive macrophages by exposure to LPS, was able to suppress CH induction when it was injected intradermally (50 ng) prior to epicutaneous application of hapten. In addition, systemic administration of larger doses of TNF alpha (200 ng) inhibited CH, whether the cytokine was injected intraperitoneally at the time of cutaneous sensitization with DNFB, or prior to ear challenge with the hapten. Importantly, when TNF alpha was injected into pinnae of DNFB-immune mice prior to elicitation of CH, local inflammatory responses were greatly exaggerated. Thus, TNF alpha shares with acute, low dose UVB radiation the following effects on CH: impairment of induction, and amplification of expression. These effects are only achieved following local treatment with these agents. We propose that TNF alpha is an important cytokine mediator of the effects of UVB on hapten-specific CH.

Animals↗
PubMed2004

Sympathetic influence on capsaicin-evoked enhancement of dorsal root reflexes in rats.

A series of experiments by our group suggest that the initiation and development of neurogenic inflammation in rats are mainly mediated by dorsal root reflexes (DRRs), which are conducted centrifugally from the spinal dorsal horn in primary afferent nocieptors. In this study, DRRs were recorded in anesthetized rats from single afferent fibers in the proximal ends of cut dorsal root filaments at the L4-L6 level and tested for responses to intradermal injection of capsaicin. Sympathectomy combined with pharmacological manipulations were employed to determine if the capsaicin-evoked enhancement of DRRs was subject to sympathetic modulation. DRRs could be recorded from both myelinated (Abeta and Adelta) and unmyelinated (C) afferent fibers. After capsaicin was injected intradermally into the plantar foot, a significant enhancement of DRRs was seen in C- and Adelta-fibers but not in Abeta-fibers. This enhancement of DRRs evoked by capsaicin injection was almost completely prevented by sympathectomy. However, if peripheral alpha1-adrenoceptors were activated by intra-arterial injection of phenylephrine, the enhancement of DRRs evoked by capsaicin could be restored, whereas no such restoration was seen following pretreatment with an alpha2-adrenoceptor agonist, UK14,304. Under sympathetically intact conditions, the enhanced DRRs following capsaicin injection could be blocked by administration of terazosin, an alpha1-adrenoceptor antagonist, but not by administration of yohimbine, an alpha2-adrenoceptor antagonist. These results provide further evidence that the DRR-mediated neurogenic inflammation depends in part on intact sympathetic efferents acting on peripheral alpha1-adrenoceptors, which augment the sensitization of primary afferent nociceptors induced by capsaicin injection, helping trigger DRRs that produce vasodilation.

Adrenergic alpha-Agonists↗