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The Editors’ Choice
The Editors’ Choice Donald Y. M. Leung, MD, PhD Harold S. Nelson, MD Stanley J. Szefler, MD
T HE J OURNAL
OF
Allergy Clinical Immunology AND
VOLUME 107
NUMBER 5
Influence of CD40 expression on atopic immune responses Using an ex vivo model co-culturing alveolar macrophages (AM) with peripheral blood CD4+ T cells, Tang et al (p 863) investigated the potential importance of cell surface epitopes on AM in influencing the outcome of T-cell immune responses to specific allergens. They demonstrated that AM from atopic asthmatics and atopic nonasthmatics had comparable levels in HLA-DR and B72 expression but that the numbers of the cells expressing B7-1 and CD40 were significantly lower in the asthmatics. AM expression of B7-1 and CD40 in atopic asthmatics continued to be lower after co-culture with allergen-stimulated CD4+ T cells and was accompanied by lower IL-12 and higher IL-5 production in comparison with the expression in atopic nonasthmatics. When monoclonal antibodies were used against B7-1 and CD40, CD40 but not B7-1 was found to relate to the AM IL-12 production. This was further confirmed through use of a neutralizing CD40 antibody in the co-cultures of atopic nonasthmatics, which caused a significant decrease in AM IL-12 production and increase in T-cell IL-5 secretion. Conversely,
A common genetic basis for idiopathic environmental intolerance and panic disorder? Idiopathic environmental intolerance (IEI), or multiple chemical sensitivity, is conceptualized as a psychologic disorder with prominent features of somatization, anxiety, and panic triggered by learned or conditioned stimuli in the environment. Proponents of a toxicogenic explanation claim, without convincing evidence, that symptoms arise from “sensitivity” to otherwise non-noxious environmental agents and that any anxiety results from the stress of living with the illness. In this issue, Binkley et al (p 887) provide preliminary but intriguing data suggesting that IEI and panic disorder might share a neurogenetic basis that would
Long-acting β-agonists and asthma exacerbations At one time there was concern on the part of some that the regular use of long-acting β-agonists might mask airway inflammation and lead to worsening asthma. Data have been accumulating to the contrary. Adding longacting β-agonists to inhaled corticosteroids appears to reduce exacerbations of asthma more than either increasing the dose of inhaled steroids or adding a
J ALLERGY CLIN IMMUNOL
CD40 expression influences the outcome of atopic immune responses.
supplementation with rhIL-12 in the co-cultures of atopic asthmatics significantly inhibited the IL-5 response. These observations suggest that pharmacologic stimulation of the antigen-presenting cell CD40 system could be effective in preventing or downregulating the asthmaphenotype immune responses in atopic individuals.
predate the onset and stress of illness and explain the shared core clinical phenotype. Cholecystokinin (CCK), an endogenous brain-gut neuropeptide, is a well-recognized panicogenic agent. An increased prevalence of CCK-B receptor allele 7 has been reported previously in panic disorder. In the pilot study of Binkley et al, an increased prevalence of panic disorder–associated cholecystokinin receptor B allele 7 was found in patients with IEI in comparison with controls (40.9% vs 9.1%, P = .037). Although the sample size was too small for these results to be considered conclusive until they are replicated in larger studies, this novel approach can be used to further characterize the neurogenetic and biologic basis of IEI. Chemically sensitive? Perhaps, but the “chemical” might be an endogenous braingut neuropeptide that contributes to panic disorder.
leukotriene receptor antagonist to the inhaled corticosteroid. In this issue, Matz et al (p 783) again report that the combination of inhaled corticosteroids and longacting β-agonists reduced the number of exacerbations of asthma. They also made an additional and quite astonishing observation: that the onset of improvement after intervention with prednisone was more rapid in those on the combination of inhaled corticosteroids and longacting β-agonists than in those on a higher dose of inhaled corticosteroids alone.
May 2001 Page 763
Different expression of chemokines in keratinocytes from patients with atopic dermatitis and keratinocytes from patients with psoriasis Atopic dermatitis (AD) and psoriasis are genetically determined disorders in which distinct T helper (TH) cell–mediated immune mechanisms have a primary role in pathogenesis. T cell–derived cytokines can stimulate keratinocytes to elaborate Interplay between TH cells and keratinocytes might favor the recruitment of different leukocyte types in chronic atopic dermatitis (A) and psoriasis (B). chemokines that attract leukocytes into the skin and thus amplify the inflammatory response. In and MCP-1 attract TH1 and TH2 lymphocytes, monocytes, this issue, Giustizieri et al (p 871) investigated the capacity of IL-4, IFN-γ, and TNF-α to modulate chemokine expresand dendritic cells. IP-10 and IL-8 are effective chemoatsion in keratinocytes cultured from patients with AD, tractants for TH1 cells and neutrophils, respectively. This patients with psoriasis, and healthy controls. AD kerstudy suggests that keratinocytes from patients with AD and atinocytes showed abnormally earlier and stronger RANTES keratinocytes from patients with psoriasis differ in their expression, whereas psoriatic keratinocytes displayed highchemokine production profile and might thus favor the er levels of IL-8, MCP-1, and IP-10. Epidermis of both recruitment of different leukocyte subsets into the skin. chronic AD and psoriasis lesions expressed RANTES and The unfolding of the genetic and molecular bases of these MCP-1. Moreover, psoriatic epidermis stained strongly for divergent keratinocyte behaviors is an important challenge IP-10 and IL-8, whereas AD epidermis did not. RANTES for future studies.
Human endotoxin susceptibility and the risk of atopy Bacterial endotoxins are important contaminants of the environment that have been related to obstructive airway diseases. Recently, it has been suggested that exposure to environmental endotoxins in early life could activate the antigen-presenting cells that are involved in the maturation of the immune system, reducing the risk of becoming atopic. In human beings, there is considerable interindividual variability in the amplitude of the response to an inhalation of endotoxin. In a study by Michel et al (p 797), individual clinical response to inhaled endotoxin was related to the inflammatory process and the atopic status. Subjects who developed fever after endotoxin
Hymenoptera sensitivity revisited It is perhaps appropriate with the coming of spring to revisit the subject of Hymenoptera sensitivity. This issue contains a wealth of practical information and a few cautionary notes on the subject. First, the workers at Johns Hopkins, led by Dr David Golden (p 897), report a prospective study of volunteers who reported systemic reactions to stings. They report that systemic reactions to sting challenges occurred as often in
inhalation had a larger increase in the systemic inflammatory response, whereas subjects with a significant lung function decrease had a larger inflammation of the airways. This suggests that the endotoxin response occurs systemically or locally in association with inflammation at their respective sites. The atopic subjects are less prone to mount a systemic inflammatory response to endotoxin. This observation reinforces the hypothesis of a mechanism linking the macrophage susceptibility to endotoxin stimulation with the increase in macrophage production of cytokines that inhibits the TH2 response and, consequently, with the risk for atopic sensitization. Given these results, reaction patterns to inhaled endotoxin might provide information about the link between innate and adaptative immunity.
those with negative as in those with positive skin tests and even in a significant number of those with negative RASTs as well. These unexpected results are the subject of an editorial by Dr Robert Reisman (p 781). Dr Goldberg and coauthor (p 902) report on their extensive experience with extending the interval in maintenance venom immunotherapy to 3 months. The rates of systemic reactions to injections and to field and intentional stings appear to establish the safety and effectiveness of this practice. Dr Wilma Light (p 925) writes in the Correspondence section about a fatal reaction to a Hymenoptera sting that occurred after discontinuation of venom immunotherapy. The implications of this report are discussed in an answering correspondence from Dr David Golden (p 925).
1/89/115373
Selected articles are indicated in the Table of Contents by EC 764 Page May 2001
J ALLERGY CLIN IMMUNOL
T HE J OURNAL
OF
Allergy Clinical Immunology AND
VOLUME 107
NUMBER 5
Influence of CD40 expression on atopic immune responses Using an ex vivo model co-culturing alveolar macrophages (AM) with peripheral blood CD4+ T cells, Tang et al (p 863) investigated the potential importance of cell surface epitopes on AM in influencing the outcome of T-cell immune responses to specific allergens. They demonstrated that AM from atopic asthmatics and atopic nonasthmatics had comparable levels in HLA-DR and B72 expression but that the numbers of the cells expressing B7-1 and CD40 were significantly lower in the asthmatics. AM expression of B7-1 and CD40 in atopic asthmatics continued to be lower after co-culture with allergen-stimulated CD4+ T cells and was accompanied by lower IL-12 and higher IL-5 production in comparison with the expression in atopic nonasthmatics. When monoclonal antibodies were used against B7-1 and CD40, CD40 but not B7-1 was found to relate to the AM IL-12 production. This was further confirmed through use of a neutralizing CD40 antibody in the co-cultures of atopic nonasthmatics, which caused a significant decrease in AM IL-12 production and increase in T-cell IL-5 secretion. Conversely,
A common genetic basis for idiopathic environmental intolerance and panic disorder? Idiopathic environmental intolerance (IEI), or multiple chemical sensitivity, is conceptualized as a psychologic disorder with prominent features of somatization, anxiety, and panic triggered by learned or conditioned stimuli in the environment. Proponents of a toxicogenic explanation claim, without convincing evidence, that symptoms arise from “sensitivity” to otherwise non-noxious environmental agents and that any anxiety results from the stress of living with the illness. In this issue, Binkley et al (p 887) provide preliminary but intriguing data suggesting that IEI and panic disorder might share a neurogenetic basis that would
Long-acting β-agonists and asthma exacerbations At one time there was concern on the part of some that the regular use of long-acting β-agonists might mask airway inflammation and lead to worsening asthma. Data have been accumulating to the contrary. Adding longacting β-agonists to inhaled corticosteroids appears to reduce exacerbations of asthma more than either increasing the dose of inhaled steroids or adding a
J ALLERGY CLIN IMMUNOL
CD40 expression influences the outcome of atopic immune responses.
supplementation with rhIL-12 in the co-cultures of atopic asthmatics significantly inhibited the IL-5 response. These observations suggest that pharmacologic stimulation of the antigen-presenting cell CD40 system could be effective in preventing or downregulating the asthmaphenotype immune responses in atopic individuals.
predate the onset and stress of illness and explain the shared core clinical phenotype. Cholecystokinin (CCK), an endogenous brain-gut neuropeptide, is a well-recognized panicogenic agent. An increased prevalence of CCK-B receptor allele 7 has been reported previously in panic disorder. In the pilot study of Binkley et al, an increased prevalence of panic disorder–associated cholecystokinin receptor B allele 7 was found in patients with IEI in comparison with controls (40.9% vs 9.1%, P = .037). Although the sample size was too small for these results to be considered conclusive until they are replicated in larger studies, this novel approach can be used to further characterize the neurogenetic and biologic basis of IEI. Chemically sensitive? Perhaps, but the “chemical” might be an endogenous braingut neuropeptide that contributes to panic disorder.
leukotriene receptor antagonist to the inhaled corticosteroid. In this issue, Matz et al (p 783) again report that the combination of inhaled corticosteroids and longacting β-agonists reduced the number of exacerbations of asthma. They also made an additional and quite astonishing observation: that the onset of improvement after intervention with prednisone was more rapid in those on the combination of inhaled corticosteroids and longacting β-agonists than in those on a higher dose of inhaled corticosteroids alone.
May 2001 Page 763
Different expression of chemokines in keratinocytes from patients with atopic dermatitis and keratinocytes from patients with psoriasis Atopic dermatitis (AD) and psoriasis are genetically determined disorders in which distinct T helper (TH) cell–mediated immune mechanisms have a primary role in pathogenesis. T cell–derived cytokines can stimulate keratinocytes to elaborate Interplay between TH cells and keratinocytes might favor the recruitment of different leukocyte types in chronic atopic dermatitis (A) and psoriasis (B). chemokines that attract leukocytes into the skin and thus amplify the inflammatory response. In and MCP-1 attract TH1 and TH2 lymphocytes, monocytes, this issue, Giustizieri et al (p 871) investigated the capacity of IL-4, IFN-γ, and TNF-α to modulate chemokine expresand dendritic cells. IP-10 and IL-8 are effective chemoatsion in keratinocytes cultured from patients with AD, tractants for TH1 cells and neutrophils, respectively. This patients with psoriasis, and healthy controls. AD kerstudy suggests that keratinocytes from patients with AD and atinocytes showed abnormally earlier and stronger RANTES keratinocytes from patients with psoriasis differ in their expression, whereas psoriatic keratinocytes displayed highchemokine production profile and might thus favor the er levels of IL-8, MCP-1, and IP-10. Epidermis of both recruitment of different leukocyte subsets into the skin. chronic AD and psoriasis lesions expressed RANTES and The unfolding of the genetic and molecular bases of these MCP-1. Moreover, psoriatic epidermis stained strongly for divergent keratinocyte behaviors is an important challenge IP-10 and IL-8, whereas AD epidermis did not. RANTES for future studies.
Human endotoxin susceptibility and the risk of atopy Bacterial endotoxins are important contaminants of the environment that have been related to obstructive airway diseases. Recently, it has been suggested that exposure to environmental endotoxins in early life could activate the antigen-presenting cells that are involved in the maturation of the immune system, reducing the risk of becoming atopic. In human beings, there is considerable interindividual variability in the amplitude of the response to an inhalation of endotoxin. In a study by Michel et al (p 797), individual clinical response to inhaled endotoxin was related to the inflammatory process and the atopic status. Subjects who developed fever after endotoxin
Hymenoptera sensitivity revisited It is perhaps appropriate with the coming of spring to revisit the subject of Hymenoptera sensitivity. This issue contains a wealth of practical information and a few cautionary notes on the subject. First, the workers at Johns Hopkins, led by Dr David Golden (p 897), report a prospective study of volunteers who reported systemic reactions to stings. They report that systemic reactions to sting challenges occurred as often in
inhalation had a larger increase in the systemic inflammatory response, whereas subjects with a significant lung function decrease had a larger inflammation of the airways. This suggests that the endotoxin response occurs systemically or locally in association with inflammation at their respective sites. The atopic subjects are less prone to mount a systemic inflammatory response to endotoxin. This observation reinforces the hypothesis of a mechanism linking the macrophage susceptibility to endotoxin stimulation with the increase in macrophage production of cytokines that inhibits the TH2 response and, consequently, with the risk for atopic sensitization. Given these results, reaction patterns to inhaled endotoxin might provide information about the link between innate and adaptative immunity.
those with negative as in those with positive skin tests and even in a significant number of those with negative RASTs as well. These unexpected results are the subject of an editorial by Dr Robert Reisman (p 781). Dr Goldberg and coauthor (p 902) report on their extensive experience with extending the interval in maintenance venom immunotherapy to 3 months. The rates of systemic reactions to injections and to field and intentional stings appear to establish the safety and effectiveness of this practice. Dr Wilma Light (p 925) writes in the Correspondence section about a fatal reaction to a Hymenoptera sting that occurred after discontinuation of venom immunotherapy. The implications of this report are discussed in an answering correspondence from Dr David Golden (p 925).
1/89/115373
Selected articles are indicated in the Table of Contents by EC 764 Page May 2001
J ALLERGY CLIN IMMUNOL