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N Yawalkar

Publications and source records attributed to N Yawalkar.

At least 37 records · Page 2Linked to original sources
PubMed2000

Down-regulation of IL-12 by topical corticosteroids in chronic atopic dermatitis.

BACKGROUND: Previous reports indicate that IL-12 may be involved in the development of chronic atopic dermatitis. However, the cellular source of this cytokine in the skin and its expression during successful treatment of the skin lesions are not known. OBJECTIVE: Our purpose was to delineate the precise in situ localization of IL-12 and its modulation under topical treatment with corticosteroids. METHODS: Skin biopsy specimens were obtained from nonlesional, lesional, and treated skin of patients with atopic dermatitis and from healthy skin of nonatopic control subjects. IL-12 was investigated by real-time quantitative reverse transcriptase-PCR and immunohistochemistry. RESULTS: Expression of IL-12 p40 mRNA was significantly enhanced in lesional skin from atopic dermatitis and strongly down-regulated after treatment with topical corticosteroids for 9 to 10 days. In contrast, similar levels of IL-12 p35 transcripts were found in all the samples without any significant differences after treatment. In addition, a strong enhancement of IL-12 immunoreactivity was observed on the mononuclear cell infiltrate in the lesional skin samples, which was also markedly reduced after treatment. IL-12 immunoreactivity was mainly located in the cytoplasm of dermal dendritic cells and macrophages as well as some Langerhans cells. CONCLUSION: Our data suggest that the enhanced local production of IL-12 in dendritic cells and macrophages may be responsible for up-regulating production of IFN-gamma in chronic lesions and strengthen the idea that IL-12 may have a pivotal role in promoting inflammation in atopic dermatitis.

Administration, Topical↗
PubMed2000

Evidence for a role for IL-5 and eotaxin in activating and recruiting eosinophils in drug-induced cutaneous eruptions.

BACKGROUND: Cutaneous drug reactions may be associated with increased numbers of eosinophils in the blood and tissue. However, the factors leading to the generation of eosinophilia have not been fully delineated. OBJECTIVE: The aim of this study was to investigate the in situ expression of IL-5, eotaxin, RANTES, monocyte chemoattractant protein 3, and IL-8 together with the appearance of eosinophils in acute cutaneous drug reactions. METHODS: Skin biopsy specimens were obtained from drug-induced maculopapular exanthems (n = 9), from normal skin of control subjects (n = 9), and from the skin of patients with psoriasis (n = 8). The in situ expression of IL-5, eotaxin, RANTES, monocyte chemoattractant protein 3, and IL-8 was analyzed by using immunohistochemistry. Furthermore, the corresponding numbers of eosinophils were determined in the blood and skin sections. RESULTS: Compared with normal skin and psoriatic skin, a significantly higher number of eosinophils was found both in the blood and tissue of patients with a drug-induced exanthem. In comparison with normal skin, immunoreactivity for IL-5 and all the chemokines was also significantly enhanced in drug-induced exanthem, whereas significant differences in psoriatic were only observed for IL-5 and eotaxin. CONCLUSION: Our data indicate that IL-5 and eotaxin may particularly contribute to the activation and recruitment of eosinophils and thereby play an important pathogenic part in the development of skin inflammation in drug-induced maculopapular exanthems.

Chemokine CCL11↗
PubMed1999

[Recommendations for choosing the right basic topical drugs in atopic dermatitis].

For the treatment of atopic dermatitis topical therapy prevails. The proper choice of the appropriate base is hereby decisive for an optimal topical therapy. It is governed by the clinical assessment of the state of the skin. Of particular importance is furthermore the persistent use of a basic treatment with ointments in order to restore skin fat and an active involvement of the patient in the choice for the appropriate preparation.

Dermatitis, Atopic↗
PubMed1999

[Drug-induced papular-purpuric gloves and socks syndrome].

The papular-purpuric "gloves and socks" syndrome (PPGSS) was first described in 1990 by Harms et al. The syndrome is characterised by fever, an itchy erythema with edema, confluent papules and purpura of the hands and feet in a "gloves and socks" distribution. The skin lesions may be associated with purpura and superficial erosions of the oral mucosa. Viral infections, in particular parvovirus B19, are the most likely trigger. In the present case PPGSS developed after taking trimethoprim/sulfamethoxazole. Since the patient developed identical symptoms after accidental re-challenge with the same drug, this case strongly suggests medications as another factor in the pathogenesis of PPGSS.

Aged↗
PubMed1999

Coprinus comatus (shaggy cap) is a potential source of aeroallergen that may provoke atopic dermatitis.

BACKGROUND: Basidiospores are universal components in the air and established as important causes of respiratory allergies. Recent reports indicate that aeroallergens may aggravate eczematous skin lesions in subjects with atopic dermatitis (AD). OBJECTIVE: The aim of the study was to investigate whether spores of Coprinus comatus, a species of basidiomycetes, may elicit delayed-type skin reactions in subjects with an atopic predilection, especially dermatitis. METHODS: Sixty-six study subjects were categorized in groups having AD or respiratory allergy with regard to the skin prick test (SPT) reactivity to C comatus extract. Twenty nonatopic individuals served as control subjects. Atopy patch tests (APTs) were performed with extract of C comatus spore containing tissue at a concentration of 1. 35 mg of protein per gram of petrolatum (Vaseline) and C comatus cap at a concentration of approximately 5 mg of protein per gram of petroleum jelly. APT reactions were evaluated after 48 and 72 hours. RESULTS: Of the subjects with AD completing the study, 12 (32%) of 38 showed a positive APT reaction, with 8 (57%) also having a positive SPT response to C comatus. Only 1 (9%) of 11 subjects with asthma had a positive SPT and APT response to C comatus. No positive test reaction was observed in the nonatopic control subjects or in subjects with respiratory allergy and negative SPT responses to C comatus. CONCLUSION: Our results demonstrate that C comatus can induce delayed-type reactions in atopic individuals, particularly in those with AD. Because spores of Coprinus species are ubiquitous, basidiomycetes have to be considered as possible aeroallergens when investigating causes of eczematous skin lesions in AD.

Adolescent↗
PubMed1999

T cell involvement in persulfate triggered occupational contact dermatitis and asthma.

BACKGROUND: Ammonium and potassium persulfates may induce a variety of cutaneous and respiratory diseases. The precise underlying mechanisms, however, are unclear. OBJECTIVE: To describe a hairdresser, who developed contact dermatitis, rhinoconjuntivitis, and bronchial asthma of delayed onset after occupational exposure to hair bleaches containing persulfate salts and to provide evidence for a common T-cell mediated mechanism responsible for the clinical manifestations. METHODS: We performed skin testing, routine histologic and immunohistochemical examination of the skin reaction after prick testing, lymphocyte proliferation analysis, nasal challenge test, and pulmonary function testing. RESULTS: The causative role of bleaching powder and ammonium persulfate was demonstrated by case history, skin tests, and a nasal challenge test. Patch tests produced a delayed cutaneous reaction to ammonium persulfate confirming contact sensitization. Prick tests with bleaching powder and ammonium persulfate were negative at 15 minutes but revealed a late skin reaction with a papule at the prick sites after 24 hours. Histologic examination of this late reaction demonstrated a perivascular infiltration comprising predominantly T lymphocytes. Further, a significant proliferation of T cells to bleaching powder was reproducibly found by a lymphocyte proliferation analysis. Nasal challenge test with bleaching powder showed a significant reduction of air flow after 24 hours. CONCLUSION: Our findings suggest that immunologic mechanism with direct involvement of T cells may not only play an important role in the pathogenesis of the cutaneous but also in the respiratory and rhinoconjunctival reactions.

Adult↗
PubMed1999

The HECA-452 epitope is highly expressed on lymph cells derived from human skin.

The cutaneous lymphocyte-associated antigen (CLA), recognized by the monoclonal antibody HECA-452, is a cell surface glycoprotein that binds specifically to E-selectin. CLA is present on most T cells at sites of cutaneous immune response and has been shown to be important in lymphocyte homing to the skin. It is expressed only by a minor subset of peripheral T cells and is absent on thymocytes. We have analysed (using a FACScan flow cytometer) the expression of CLA on human lymph cells derived from normal skin, from ultraviolet (UV)-irradiated skin and from allergic contact dermatitis. Whereas in the peripheral blood CLA was expressed on < 20% of CD4 +, CD8 + and CD56 + cells (natural killer cells), > 60% of CD4 +, CD8 + and CD56 + cells isolated from skin-derived lymph expressed CLA. Furthermore, > 90% of CD1a + dendritic lymph cells were positive for CLA. UV irradiation of the skin and induction of an allergic contact dermatitis did not change CLA expression on lymph cells, although lymph flow and cell output increased. These results provide further evidence for an important role of CLA in cell homing to the skin.

Adult↗
PubMed1999

T-cell reaction to local anaesthetics: relationship to angioedema and urticaria after subcutaneous application--patch testing and LTT in patients with adverse reaction to local anaesthetics.

BACKGROUND: Local anaesthetics are known to elicit T-cell reactions after epicutaneous application, namely contact dermatitis. In addition, adverse reactions like urticaria and angioedema are rather common after submucosal or subcutaneous injection. The pathogenesis of these side-effects, which appear frequently hours after application, is unknown, but thought to be not immunoglobulin E-mediated, since immediate skin tests are mostly negative. OBJECTIVES: We investigated whether patients who developed urticaria and angioedema after subcutaneous application have a T-cell sensitization to local anaesthetics, which might be responsible for the symptoms. METHODS: Twenty patients with generalized and/or local cutaneous reactions after LA were examined with intradermal testing using a standard panel of six LAs and patch testing using between seven and nine LAs in vaseline and four LAs in PBS. In 10 patients, a lymphocyte transformation test (LTT) was performed. RESULTS: Only 2/20 patients had an immediate skin reaction (positive intradermal test), whereas 6/20 patients had a positive delayed skin reaction (positive patch test). In 6/10 subjects the LTT was positive. CONCLUSIONS: Delayed appearance of urticaria and angioedema after subcutaneous application of local anaesthetics may be related to a T cell- mediated sensitization, which might be detected by patch testing or LTT.

Adolescent↗
PubMed1999

Enhanced expression of eotaxin and CCR3 in atopic dermatitis.

Chemokines are thought to play an important part in the development of inflammation in atopic dermatitis. Eotaxin, a CC chemokine, is a potent chemoattractant and activator of human eosinophils, basophils and Th2 lymphocytes which acts via the chemokine receptor CCR3. We studied the expression of eotaxin and CCR3, as well as MCP-3, MIP-1alpha and interleukin-8, in atopic dermatitis and normal skin by immunohistochemistry and nested reverse transcriptase-polymerase chain reaction. Skin biopsy specimens were obtained from nonlesional and lesional skin of patients with atopic dermatitis and of nonatopic controls. Immunoreactivity and transcripts of eotaxin and CCR3 were significantly increased in lesional skin from atopic dermatitis, but not in nonatopic controls. In nonlesional atopic dermatitis samples CCR3 expression was also significantly increased at the mRNA and protein level, whereas eotaxin was increased at the mRNA level only. No significant difference in the expression of MCP-3, MIP-1alpha, and interleukin-8 was observed between skin samples from atopic dermatitis and nonatopic controls. The enhanced local production of eotaxin may lead to the recruitment of eosinophils and T lymphocytes, which both express CCR3 and contribute to the initiation and maintenance of inflammation.

Adolescent↗
PubMed1999

Drug-induced linear IgA bullous dermatosis associated with ceftriaxone- and metronidazole-specific T cells.

BACKGROUND: Previous reports indicate that various drugs may induce linear IgA bullous dermatosis (LABD). The role of T cells and T-cell-derived cytokines in the pathomechanism of such skin lesions, however, has remained unclear. OBJECTIVE: To describe a case of LABD induced by ceftriaxone and metronidazole in an 80-year-old female suffering from cholelithiasis with concomitant cholecystitis and provide evidence that drug-specific T cells and their cytokines may contribute to the development of LABD lesions. METHODS: We performed flow cytometry analysis of peripheral blood T cells during LABD, epicutaneous testing (scratch-patch) and lymphocyte proliferation analysis (LTT) with the suspected drugs, routine histological and immunohistochemical examination of the acute skin lesions during LABD as well as of the positive epicutaneous test reactions and measurement of cytokines (IL-4, IL-5, IL-10, TNF-alpha, IFN-gamma) in the supernatant of the LTT cultures. RESULTS: An increased number mainly of activated CD8+ cells was detected in the peripheral blood during LABD. T cell sensitization to ceftriaxone and metronidazole was confirmed by epicutaneous testing and LTT, indicating that these methods may be useful in identifying the causative drugs. Enhanced cytokine levels, particularly of IL-5, were found in the supernatant of the LTT stimulated with ceftriaxone and metronidazole. Furthermore, in situ expression of IL-5 was confirmed in the patient's skin lesions by immunohistochemistry. CONCLUSION: Our findings suggest that in addition to IgA antibodies drug-specific T cells and their subsequent release of cytokines may play an important role in the pathogenesis of drug-induced LABD.

Aged↗
PubMed1999

Distinct serum cytokine levels in drug- and measles-induced exanthema.

BACKGROUND: Macular or maculopapular skin reactions are frequent events in drug allergy as well as in viral infections. Clinically, the differentiation may be difficult in the absence of a clear relationship to drug intake or failure to detect virus-specific antibodies of the IgM class. Studies on drug-specific T cell lines and T cell clones isolated from drug-allergic patients have suggested that these cells may represent a significant source of IL-5. On the other hand, viral infections are frequently associated with elevated IFN-gamma levels. OBJECTIVE: Determination of serum-cytokine levels to differentiate between drug- and virally induced skin eruptions. PATIENTS: 18 patients suffering from acute drug allergy and 19 patients with acute measles, rubella or parvovirus infection. MEASUREMENTS: Cytokine-ELISA (IL-5, IL-4 and IFN-gamma) of sera collected during acute drug allergy or during acute measles, rubella or parvovirus infection. RESULTS: In 12/18 patients with drug allergy, IL-5 and/or IL-4 were elevated. A significant correlation (r(Spearman) = 0.84) between IL-5 serum levels and eosinophil counts in the blood was found. No correlation was detected between IL-4 and blood eosinophilia or between IL-4 and IL-5 levels. After remission, IL-5 and IL-4 decreased to undetectable levels. IFN-gamma on the other hand was not measurable in patients with drug allergy while elevated IFN-gamma serum levels were detected in 17/19 patients with measles, rubella or parvovirus infection; 2 patients with acute virus infection had elevated IL-5, and/or IL-4 and IFN-gamma levels. CONCLUSION: These data underline the distinct pathogenesis of these morphologically similar exanthemas and suggest that the combined analysis of eosinophilia in the blood, IL-4 and IFN-gamma might help in differentiating skin eruptions.

Adolescent↗
PubMed1998

Interleukin-12 expression in human afferent lymph derived from the induction phase of allergic contact dermatitis.

Recent reports suggest that production of interleukin-12 (IL-12) by dendritic cells and keratinocytes may play an important part in contact hypersensitivity reactions. In the present study we investigated mRNA and protein expression of IL-12 in human skin lymph derived from normal untreated skin (n = 5) and from the induction phase of allergic contact dermatitis (CD) (n = 5). mRNA levels were determined at various time points in the lymph cells by a nested reverse transcriptase-polymerase chain reaction method. Time course analysis reproducibly revealed a constitutive expression of both IL-12 p40 and p35 mRNA in the migrating lymph cells in all volunteers. However, no enhancement of the IL-12 mRNA signal was found during the induction phase of allergic CD. Furthermore, as determined by a sensitive ELISA technique, IL-12 protein was not detectable in 60 lymph samples derived from normal untreated skin or in 68 lymph samples obtained during the induction phase of allergic CD at any time point of the lymph cannulation. In conclusion, our findings indicate that no significant protein levels of IL-12 are washed out from the skin into the afferent lymph or are produced and released by migrating lymph cells during the induction phase of allergic CD in vivo.

Adult↗
PubMed1998

T-cell-mediated cytotoxicity against keratinocytes in sulfamethoxazol-induced skin reaction.

BACKGROUND: The incidence of skin rashes or erythema multiforme to sulfamethoxazole in exposed patients is about 3%. Among patients with acquired immunodeficiency syndrome the risk is approximately 10 times higher. The pathogenesis of these reactions and the reason for the increased frequency in HIV infections are not understood. OBJECTIVE: To investigate drug specific T-cell-mediated cytotoxicity in sulfamethoxazole- induced skin reactions. METHODS: Specific T-cell lines and T-cell clones generated from a donor who developed a skin rash to sulfamethoxazole were assessed with a standard 4 h 51Cr cytotoxicity assay in the presence or absence of soluble sulfamethoxazole. B lymphoblasts and keratinocytes with and without interferon gamma pretreatment were used as target cells. Selective blockers of FasL/Fas and perforin-mediated killing and immunostaining for perforin were used to evaluate the involvement of the different cytolytic pathways. RESULTS: CD4+ and CD8+ sulfamethoxazole specific T-cell clones showed a drug-specific and MHC-restricted cytotoxicity against autologous B lymphoblasts in the presence of soluble sulfamethoxazole. Keratinocytes, if pretreated with interferon gamma, were specifically killed predominantly by CD4+ T-cell clones. Specific T-cell clones of both CD4+ and CD8+ phenotype showed a strong immunoreactivity for perforin and the cytotoxicity was blocked by concanamycin A which suggests a perforin-mediated killing. CONCLUSION: Perforin-mediated killing of autologous keratinocytes in the presence of soluble sulfamethoxazole by drug-specific CD4+ lymphocytes may be a pathway for generalized drug-induced delayed skin reactions. The requirement of interferon gamma pretreatment of keratinocytes for efficient specific killing might explain the increased frequency of drug allergies in generalized viral infections like HIV, when interferon gamma levels are elevated.

CD4-Positive T-Lymphocytes↗
PubMed1998

Expression of interleukin-12 is increased in psoriatic skin.

Although the precise underlying pathomechanisms of psoriasis have not been fully elucidated, previous reports suggest that T helper 1-type cytokines are critically involved in the pathogenesis of this disease. Interleukin-12 (IL-12), a heterodimeric cytokine, has been suggested to play a major role in the development of T helper 1 cell responses. In this study, the presence of IL-12 mRNA and protein was investigated in normal human skin as well as nonlesional and lesional psoriatic skin. Messenger RNA levels were determined in biopsy specimens by a standard and a nested reverse transcriptase-polymerase chain reaction method. Additionally, IL-12 protein expression was analyzed in situ by immunohistochemistry using an antibody recognizing IL-12 p70. Whereas specific transcripts for IL-12 p35 were reproducibly detected without any significant differences in all samples, enhanced IL-12 p40 mRNA signals were only found in lesional psoriatic skin as compared with normal and nonlesional psoriatic skin. Furthermore, immunoreactivity for IL-12 p70 was markedly increased in the psoriatic skin lesions and was predominantly expressed on mononuclear cells in the dermis. In conclusion, our data suggest a critical role for IL-12 in promoting and maintaining T cell activation and inducing T helper 1-type cytokines such as interferon-gamma in psoriasis. We speculate that IL-12 might be a key cytokine in the pathogenesis of psoriasis.

Adult↗
PubMed1998

Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo.

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-alpha and IFN-gamma) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.

Adolescent↗
PubMed1997

Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localizing with eosinophils.

BACKGROUND: The chemokine eotaxin is produced at sites of allergic inflammation, binds selectively to the chemokine receptor CCR3 and attracts eosinophil and basophil leukocytes, which express high numbers of this receptor. Responses of T lymphocytes to eotaxin have not been reported so far. We have investigated the expression of CCR3 in T lymphocytes and analysed the properties and in vivo distribution of T lymphocytes expressing this receptor. RESULTS: In search of chemokine receptors with selective expression in T lymphocytes, we have isolated multiple complementary DNAs (cDNAs) encoding CCR3 from a human CD4+ T-cell cDNA library. T-lymphocyte clones with selectivities for protein and non-protein antigens were analysed for expression of CCR3 and production of Th1- and Th2-type cytokines. Of 13 clones with surface CCR3, nine secreted enhanced levels of interleukin-4 and/or interleukin-5, indicating that CCR3 predominates in Th2-type lymphocytes. CCR3+ T lymphocytes readily migrated in response to eotaxin, and showed the characteristic changes in cytosolic free calcium. Immunostaining of contact dermatitis, nasal polyp and ulcerative colitis tissue showed that CCR3+ T lymphocytes are recruited together with eosinophils and, as assessed by flow cytometry, a large proportion of CD3+ cells extracted from the inflamed skin tissue were CCR3+. By contrast, CCR3+ T lymphocytes were absent from tissues that lack eosinophils, as demonstrated for normal skin and rheumatoid arthritis synovium. CONCLUSIONS: We show that T lymphocytes co-localizing with eosinophils at sites of allergic inflammation express CCR3, suggesting that eotaxin/CCR3 represents a novel mechanism of T-lymphocyte recruitment. These cells are essential in allergic inflammation, as mice lacking mature T lymphocytes were insensitive to allergen challenge. Surface CCR3 may mark a subset of T lymphocytes that induce eosinophil mobilization and activation through local production of Th2-type cytokines.

Cell Movement↗