Biomedical subjects

C von Allmen

Publications and source records attributed to C von Allmen.

At least 19 recordsLinked to original sources

PubMed2001

ICOS ligand costimulation is required for T-cell encephalitogenicity.

The interaction of ICOS with its ligand on APC provides a costimulatory signal to previously activated T-cells. In these studies, we blocked the ICOS:ICOS ligand interaction with ICOS-Ig during the in vitro activation of MBP-reactive transgenic CD4(+) T-cells. The presence of ICOS-Ig in these cultures inhibited the ability of the transgenic T-cells to transfer EAE, although they entered the brains of the recipient mice. ICOS-Ig increased apoptosis in the transgenic T-cells, especially in the memory population. This enhanced apoptosis was accompanied by an increase in the BAX/BCL-2 mRNA ratio. ICOS-Ig did not prevent IL2 production, demonstrating that IL-2 production is ICOS ligand independent. IFN-gamma and IL-10 production by the transgenic T-cells, however, was suppressed. Finally, ICOS-Ig injection into mice after the first signs of EAE ameliorated clinical disease. Therefore, ICOSL provides a signal distinct from CD28 costimulation that is required for the activation and viability of encephalitogenic T-cells.

Animals↗

PubMed2000

Sequential patterns of inflammatory events during developing and expressed skin late-phase reactions.

BACKGROUND: Although there has been much study of the histologic features of the late-phase reactions (LPR) seen 6 to 24 hours after intradermal injection of allergens, much less is known about the events occurring during development of such LPR. OBJECTIVE: Our purpose was to compare sequential gross and histologic inflammatory responses during developing skin LPR within 6 hours after challenge. METHODS: Gross reactions were measured and biopsy specimens obtained at 20 minutes and 1, 2, and 6 hours after intradermal allergen (Ag) and buffer diluent control (B) injections in 7 atopic subjects with known immediate and LPR. Inflammatory cell responses were compared, as detected by immunohistochemistry in Ag and B sites. These findings were then compared with those at 24 hours. RESULTS: Gross LPR evolved without a hiatus from the immediate wheal responses over the next 6 hours (P =.04 vs that in B sites) and then decreased by 24 hours. Prominent PMN accumulation started by 20 minutes, peaking at 1 hour (P <.01). Eosinophil accumulation was significant, starting at 1 hour (P <.001) and peaking at 6 hours (P < .001). Many eosinophils were activated (EG(2)(+)). T-cell accumulation started at 2 hours (P =.01) and was most prominent at 24 hours. The frequency of vessels expressing E-selectin increased at 1 hour (P <.005), correlating with the degree of local PMN accumulation. The frequency of vessels expressing vascular cell adhesion molecules started increasing at 6 hours (P = .02), well after eosinophil accumulation was prominent. CONCLUSIONS: Skin LPR is characterized by evolution of a gross indurated reaction from the immediate whealing response over the first 6 hours after intradermal Ag challenge, with an early accumulation of PMN and eosinophils, not directly attributable to lymphocyte entry or vascular cell adhesion molecule expression. Likely, multiple other factors may also play roles in the complex pathogenesis of LPR.

Adult↗

PubMed1999

Comparative effects of antilactoferrin antibodies and tumor necrosis factor on neutrophil adherence to matrix proteins.

Neutrophil adherence to matrix proteins likely plays an important role in inflammatory responses. Antineutrophil cytoplasm antibodies may activate neutrophils in certain diseases. Using an in vitro method that allows simultaneous quantitation of neutrophil adherence and superoxide secretion, we compared the effects of antibodies against neutrophil granule proteins and tumor necrosis factor alpha (TNF-alpha), a known neutrophil agonist. Antilactoferrin antibodies but not antielastase or antimyeloperoxidase antibodies stimulated increased adherence to fibronectin and laminin similar in degree to that induced by TNF-alpha. This, but not the simultaneous superoxide secretion, was inhibited in the presence of anti-CD18 antibodies. Humoral immune responses to lactoferrin, likely expressed on the neutrophil surface, can activate neutrophils in proinflammatory responses that may be pathogenic.

Antibodies↗

PubMed1998

Patterns of inflammatory responses following rechallenge of skin late-phase allergic reaction sites.

BACKGROUND: Previous studies have suggested altered responses to repeat skin tests in the sites of IgE-mediated late-phase reactions (LPRs) induced within the previous 48 hours. To explore the possible modulation of LPRs in such rechallenge sites, we compared inflammatory responses in skin chambers induced over previous LPR and control sites. METHODS: Skin blisters were induced and unroofed in 12 human subjects over two sites of previous LPRs induced by intradermal injection of pollen antigens 24 hours or 48 hours earlier and two sites previously injected with buffer diluent (B). Skin chambers containing the same antigens were appended to one intradermal antigen site (called Ag/Ag) and one intradermal B site (B/Ag), and B-containing chambers were placed over antigen (Ag/B) and B (B/B) intradermal sites. Fluids were collected after the first and the second through fifth hours of challenge. RESULTS: In skin chamber challenges 24 hours after the intradermal injection, there was no significant difference after the first hours between the Ag/Ag or B/Ag sites in either histamine or tryptase levels; both were significantly higher than at Ag/B or B/B sites (p < 0.01). The same pattern of events was seen in fluids obtained from the second through fifth hours. The same pattern of findings was seen in examination of levels of the total leukocyte accumulation, total eosinophil accumulation, and frequency of activated (EG2+) eosinophils. Levels of lactoferrin, released from activated neutrophils, and eosinophil cationic protein, released from activated eosinophils, were also similar at Ag/Ag and B/Ag sites; both were significantly higher than at B/B sites, whereas levels at Ag/B sites were intermediate between those found at B/Ag and B/B sites. The pattern of events in skin chamber challenges 48 hours after intradermal injection was similar to that seen at 24 hours, except that levels of inflammatory mediators/cells in Ag/B sites were more intermediate between the B/Ag and B/B sites. CONCLUSION: There is no significant alteration of mediator or inflammatory cell responses after antigen rechallenge of previous LPR sites when compared with those found in antigen challenge of non-LPR sites.

Chymases↗

PubMed1998

Comparison of inflammatory events in skin sites with and without cutaneous late-phase reactions after prominent immediate IgE-mediated responses.

BACKGROUND: A number of inflammatory events have been detected in skin chambers overlying sites of developing late-phase reactions (LPR) to pollen antigens in sensitive subjects. However, the pathogenic significance of such events is still unclear. OBJECTIVE: We sought to compare inflammatory responses and cytokine levels in skin chambers that overlie sites of antigen challenge in individuals with and individuals without LPRs after immediate wheal responses of similar intensity. RESULTS: Early histamine releases at antigen sites were similar in eight subjects with LPR (+/+ group) and eight subjects without LPR (+/- group). However, histamine releases during hours 2 through 5 of antigen challenge were significantly greater in the +/+ subjects than in the +/- subjects. Total exuding leukocytes; percent eosinophils; and levels of eosinophil cationic protein, lactoferrin, and IL-8 were significantly greater at antigen versus buffer control challenge sites in both the +/+ and +/- groups, with no significant differences between the groups. IL-1 and IL-6 levels were not greater at antigen sites than at buffer sites. CONCLUSIONS: The only significantly greater antigen-induced response detected in +/+ subjects than in +/- subjects was in later histamine release, which is possibly a marker of other inflammatory responses because histamine itself does not induce LPRs. Other inflammatory events assessed may be somewhat greater in +/+ subjects, but not significantly so.

Antigens↗

PubMed1998

Comparison of inflammatory events during developing immunoglobulin E-mediated late-phase reactions and delayed-hypersensitivity reactions.

To compare cellular and mediator responses in early developing late-phase skin reactions (LPR) and delayed-hypersensitivity (DH) reactions in the same subjects, responses in skin chambers overlying sites of challenge with pollen antigen and Candida albicans antigens were compared in six humans with demonstrated prominent LPR and DH responses. Histamine levels in overlying chamber fluids at 1 h were much higher at LPR than at DH sites (P = 0.002). After the next 4 h, leukocyte exudation was higher at LPR than at DH sites (P = 0.005). Most leukocytes were activated neutrophils with greater frequency of superoxide-secreting cells and released lactoferrin at LPR than at DH sites (P = 0.01 and P = 0.02, respectively). The frequency of exuding eosinophils was higher, but not significantly so (P = 0.5), at LPR sites. Although significantly more eosinophils at LPR sites were activated (P = 0.02), the levels of released eosinophilic cationic protein were not significantly higher at LPR sites (P = 0.09). The levels of interleukin-8 (IL-8), but not IL-6, were greater at LPR than at DH sites. During the first 5 h of challenge there was greater mast cell activation and subsequent exudation of activated neutrophils at sites of developing LPR than at DH sites, possibly related to greater local IL-8 levels. The frequency of activated eosinophils was also greater at LPR sites. These different initial inflammatory responses could play a role in determining expression of LPR or DH reactions.

Allergens↗

PubMed1997

Cellular inflammatory responses during immediate, developing, and established late-phase allergic cutaneous reactions: effects of cetirizine.

BACKGROUND: In some previous studies, the antihistamine cetirizine has inhibited both developing (at 6 hours) and established (at 24 hours) gross late-phase skin reactions (LPR) to pollen antigens, possibly relevant to clinical drug effects. However, the effects of cetirizine at the histologic level require further definition. OBJECTIVE: To characterize cetirizine effects on gross and histologic inflammatory events from 20 minutes to 24 hours after intradermal antigen challenge in sensitive patients. METHODS: Gross and histologic responses to intradermal pollen antigen, codeine, histamine, and buffer diluent were assessed during randomized 7-day treatments with cetirizine and placebo. Accumulated neutrophils, eosinophils, activated (EG2+) eosinophils, and T lymphocytes were quantitated. The degrees of extracellular deposition of lactoferrin from neutrophils and eosinophilic cationic protein (ECP) from eosinophils were also assessed. RESULTS: During placebo treatment, wheal-and-flare responses were significantly greater to antigen at 20 minutes (p < 0.01) and induration at 6 hours (p < 0.01) at antigen challenge sites than at buffer diluent sites. During cetirizine treatment, these wheal-and-flare responses to antigen were inhibited significantly (p < 0.01) but gross LPRs were not affected. During placebo treatment, significantly more cells per high-power field were found in antigen sites than in buffer sites of neutrophils at 20 minutes (p < 0.01) and 24 hours; than in eosinophils at 20 minutes, 6 hours, and 24 hours (p < 0.01 for each); than in EG2+ cells at 20 minutes (p = 0.004), 6 hours (p = 0.001), and 24 hours (p = 0.02); and at T lymphocyte sites at 24 hours (p = 0.001). Extracellular deposition of lactoferrin and ECP was significantly greater at antigen sites than at buffer sites at 6 and 24 hours. Cetirizine treatment had no significant effect on these responses. CONCLUSION: Neutrophils, eosinophils, and T lymphocytes were persistently more common at antigen sites than at buffer sites through 24 hours. Many of these neutrophils and eosinophils were activated, releasing more lactoferrin and ECP into the extracellular dermis for at least 24 hours after antigen challenge. Cetirizine inhibited gross immediate responses to antigen, but not the gross LPR nor the cellular inflammatory responses seen in such LPR sites.

Administration, Cutaneous↗

PubMed1997

Cellular inflammatory responses and mediator release during early developing late-phase allergic cutaneous inflammatory responses: effects of cetirizine.

BACKGROUND: Events in developing cutaneous late-phase allergic reactions can be characterized by a combination of skin chamber and biopsy approaches. In some previous studies, cetirizine reportedly inhibited mediator release and/or inflammatory cell responses in late-phase reactions. OBJECTIVE: This study was carried out to determine the effects of cetirizine on early late-phase reactions by using skin chamber and skin biopsy specimens. METHODS: Skin chamber responses during a 6-hour challenge with pollen antigens were assessed in 15 sensitive subjects during randomized, crossover treatment with cetirizine (20 mg/day) or placebo for 7-day periods with measurements of humoral and cellular components. Biopsy specimens of the underlying dermis were obtained. RESULTS: During cetirizine treatment, there was significant (p < 0.01) inhibition of immediate wheal and flare reactions to pollen antigens (34, 46%), codeine (41, 65%), and histamine (38, 68%). However, gross late-phase reactions at 6 hours were unaffected. During both cetirizine and placebo treatment, there was significantly greater accumulation at antigen sites in: (1) skin chamber levels of histamine, total cells, lactoferrin, and eosinophil cationic protein; (2) eosinophils (total and activated) on appended cover glasses; (3) deposition of lactoferrin and eosinophil cationic protein in the underlying dermis. However, these responses were not significantly different during cetirizine treatment compared with placebo treatment periods. CONCLUSION: A persistent pattern of inflammatory cell accumulation with release of granule proteins during early late-phase reactions was unaffected by cetirizine treatment.

Antigens↗

PubMed1995

Products of arachidonic acid metabolism and the effects of cyclooxygenase inhibition on ongoing cutaneous allergic reactions in human beings.

BACKGROUND: There have been conflicting reports about the effects of inhibition of arachidonic acid metabolism on early- and late-phase cutaneous reactions. We re-examined this question with a unique nonsteroidal antiinflammatory drug, tenidap sodium. Tenidap sodium has been demonstrated in in vitro studies to inhibit cyclooxygenase, lipoxygenase, and cytokine production (interleukin-1, interleukin-6, tumor necrosis factor-alpha). METHODS: In a double-blind, randomized, crossover study, seven pollen-sensitive subjects ingested tenidap (120 mg, by mouth, daily) and placebo for 9 days with a 3-week washout period between treatments. On the eighth day they underwent allergen skin testing, measurable for up to 12 hours, and on the ninth day they underwent 5-hour skin chamber exposures to allergen and buffer. Chamber fluids were analyzed for cellular content, neutrophil granule protein release, cyclooxygenase and lipoxygenase arachidonic acid metabolites, histamine, and tryptase. RESULTS: Tenidap did significantly inhibit cyclooxygenase metabolites at both antigen and buffer sites but had no effect on histamine, tryptase, lipoxygenase metabolites, or granulocyte infiltration. Neutrophil granule release of lactoferrin was lower at the antigen site during tenidap administration, but there was no reduction of elastase release. Prostaglandin E2 and leukotriene E4 increased significantly at antigen sites compared with buffer sites during placebo administration and were the most prominent arachidonic acid metabolites detected. CONCLUSION: Tenidap, despite inhibiting cyclooxygenase release at antigen sites, had no effect on skin test responses to antigen or on antigen-induced mediator release or granulocyte infiltration. We conclude that cyclooxygenase metabolites are not important in the development of an allergic cutaneous inflammatory response.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1993

Comparison of cytosolic calcium shifts, superoxide generation, and lactoferrin secretion in the neutrophils of atopics and nonatopics.

We previously found that platelet-activating factor (PAF) stimulated greater lactoferrin secretion by neutrophils of atopics than nonatopics. To help understand underlying mechanisms, we compared agonist-stimulated lactoferrin secretion with another response, superoxide generation, to determine whether there is a global alteration in the reactivity of atopic neutrophils to these stimuli. We also determined Ca2+ mobilization in such neutrophils because such mobilization is a signaling pathway for both superoxide generation and granule content exocytosis. Although PAF again stimulated greater lactoferrin secretion in atopic than in nonatopic neutrophils, the peak superoxide secretion and cytosolic Ca2+ mobilization were not significantly different in atopics and nonatopics. Leukotriene B4-induced superoxide secretion and cytosolic Ca2+ shifts were also similar in atopics and nonatopics. These findings suggest that (1) the enhanced PAF-induced lactoferrin secretion in atopic neutrophils is not a reflection of greater PAF binding or broad-based cell hyperreactivity and (2) a selective signaling pathway in atopic neutrophils may be responsible for the enhanced lactoferrin secretion. These findings may be relevant to in vivo events because we have found increased PAF and lactoferrin release in skin chambers overlying immunoglobulin E-mediated human skin reactions.

Calcium↗

PubMed1993

The effects of gender on allergen-induced histamine release in ongoing allergic cutaneous reactions.

BACKGROUND: Marked variability in the amount of histamine released in the first hour of ongoing cutaneous reactions has been noted. This variability occurs even among subjects with similar degrees of skin test reactivity to antigen. METHODS: To determine gender effects on mediator release, we retrospectively compared: (1) skin chamber histamine release after a 0 to 1-hour and 1 to 5-hour exposure to antigen; (2) neutrophil accumulation after 5 hours of antigen exposure and skin test reactivity to antigen, histamine, and codeine in 91 male and 60 female subjects. RESULTS: There was no difference in skin test reactivity to antigen, histamine, or codeine between male and female subjects. However, in the group as a whole, male subjects released higher amounts of histamine in the first hour (74 +/- 4 ng/ml) than female subjects (55 +/- 4 ng/ml), (p < 0.01). When subjects were matched for equivalent skin reactivity to antigen, male subjects who were sensitive to 10 PNU/ml and 1 PNU/ml released more histamine (67 +/- 9 ng/ml and 82 +/- 9 ng/ml) than female subjects (51 +/- 7 ng/ml and 55 +/- 7 ng/ml) (p < 0.05 and < 0.01). In the most sensitive subjects, those with skin sensitivity to 0.01 PNU/ml of antigen, there was not a significant difference between the histamine release in the first hour in male (79 +/- 12 ng/ml) or female (69 +/- 9 ng/ml) subjects. No difference was observed between male and female subjects in either neutrophil or histamine accumulation in the 1- to 5-hour period. CONCLUSIONS: Since the first hour release of histamine is secondary to mast cell activation and the 1- to 5-hour histamine release is secondary to basophil activation, we conclude that the gender of the subject influences the degree of in vivo antigen-induced histamine release from mast cells.

Adolescent↗

PubMed1993

Fibrin formation during ongoing cutaneous allergic reactions: comparison of responses to antigen and codeine.

BACKGROUND: Fibrin formation, assessed by fibrinopeptide A levels, was evaluated over a 5-hour period at skin chamber sites challenged continuously with pollen antigen or codeine in 10 reactive individuals. METHODS: The levels of fibrinopeptide A at antigen sites were compared with those at sites challenged with buffer diluent alone or with codeine for the first 3 hours, followed by antigen challenge during the subsequent 2 hours. RESULTS: Findings showed: (1) fibrinopeptide A levels were higher at antigen challenge sites than at codeine challenge sites by the third hour, with these levels at both sites greater than those at buffer sites; (2) antigen challenge of the previous codeine sites during the third to fifth hours led to a further increase in fibrinopeptide A levels; (3) fibrinopeptide A levels correlated with chamber fluid immunoglobulin G levels but not with chamber fluid histamine levels. CONCLUSIONS: Because antigen and codeine both activate mast cells prominently, these findings suggest that other factors play a role in the persistent fibrin formation at allergic skin reaction sites. Because antigen activates both basophils and mast cells and codeine only activates mast cells, we conclude that both basophils and mast cells contribute to the persistent fibrin formation at sites of allergic reactions.

Antigens↗

PubMed1992

Activation of the coagulation pathway during ongoing allergic cutaneous reactions in humans.

The levels of histamine, fibrinopeptide A (FPA), and IgG were determined in chamber fluids overlying sites of antigen versus buffer incubation for up to 7 hours in seven atopic and four antigen-nonreactive subjects. Significant increases in histamine were observed at antigen versus buffer sites in the atopic subjects throughout the 7-hour period. FPA and IgG levels were higher in antigen than in buffer sites from 0 to 5 hours in the atopic subjects. Furthermore, FPA levels correlated with the magnitude of induration at 6 hours after antigen injection in atopic subjects. There were no differences in the levels of histamine, FPA, or IgG at antigen versus buffer sites in the skin test-negative subjects. We suggest that the combination of vascular leakage of proteins, induced by vasoactive mediator release, and activation of these proteins during ongoing cutaneous reactions is responsible for fibrin formation that contributes to the pathophysiology of late-phase allergic responses in the skin.

Adult↗

PubMed1992

Effects of skin-chamber fluids from human allergic reactions on neutrophil activation.

We have found activated neutrophils (PMNs) in skin chambers overlying the site of ongoing human allergic reactions. To determine whether this activation is due to component(s) released early in these IgE-mediated reactions, we investigated the in vitro effects of skin chamber fluids (CF) on resting blood PMNs. These skin CF had been previously obtained, at different time periods, at pollen-antigen-challenged or buffer-control-challenged sites in sensitive human subjects. PMNs incubated with CF obtained during the first hour of antigen challenge (first-hour CF) generated significantly more superoxide (O2-) than spontaneous production (p less than 0.001) and more than PMNs incubated with first-hour buffer-site CF (p less than 0.002). A pattern similar to O2- generation was observed in lactoferrin secretion during the incubation of the three cell aliquots described above (p less than 0.001). After these incubations, the subsequent responsiveness of the PMNs present in the cell buttons to opsonized zymosan, a PMN activator, was assessed. PMNs previously incubated with first-hour CF generated significantly more net O2- in response to opsonized zymosan than did PMNs previously incubated with first-hour buffer-site CF (p less than 0.001) or buffered saline (p less than 0.001). Again, a similar difference in the patterns of net lactoferrin secretion was observed (p less than 0.02). These events were not associated with PMN damage. Analogous studies with CF previously obtained during the second- to first-hour of antigen or buffer challenge stimulated much less than first-hour CF. We conclude that one or more components released early in IgE-mediated skin reactions can activate PMNs. The nature of the activating component(s) is unknown, with no evidence of activation by histamine, antigen, or other components found to date in first-hour CF.

Adult↗

PubMed1991

Release of eosinophil granule proteins during IgE-mediated allergic skin reactions.

To determine whether the eosinophil (EOS), a prominent component of human allergic skin reactions, releases its potentially pathogenic components in vivo, we appended collection chambers to the bases of unroofed skin blisters and challenged the sites for varying time periods with either pollen antigen (Ag) or buffer (B)-control solutions. In seven sensitive subjects, continuous challenge with pollen Ag consistently induced release of more major basic protein (MBP) and eosinophil-derived neutrophil (EDN) than did B solution. Low levels of both MBP and EDN were observed during the first hour with increased accumulation during the second to fifth hour. Comparison of Ag- versus B-challenged site responses in individual subjects demonstrated significantly higher levels of both MBP and EDN at Ag than at B sites during the second to fifth hour. Levels of both MBP and EDN in the second to fifth hour correlated significantly with histamine release in the same sites in the first hour (r = 0.66 and 0.83, respectively). Imprints of the skin bases of the chambers after 5 hours demonstrated variable numbers of EOS at the Ag-challenged sites and only occasional EOS at the B-challenged sites; most cells on the skin bases were neutrophils. However, immunofluorescence localization of MBP in biopsy specimens of the blister bases revealed striking extra cellular MBP deposition. These findings indicate that EOS components accumulate in vivo in IgE-mediated human skin reactions, even when prominent EOS accumulation is not visualized, possibly because the EOS are degranulated in the allergic-reaction site. Release of EOS components in these reactions may be linked to earlier mast cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

In vivo antigen-induced cutaneous mediator release: simultaneous comparisons of histamine, tryptase, and prostaglandin D2 release and the effect of oral corticosteroid administration.

To determine if basophils were responsible for the persistent release of histamine during continuous antigen (Ag) administration in the skin, we compared the release of histamine, tryptase, and prostaglandin D2 (PGD2) at sites of continuous (5 hours) and intermittent Ag and codeine skin-chamber challenge in the skin of 16 atopic and four nonatopic subjects. In addition, we compared the release of these three mediators at sites of continuous Ag challenge in five subjects during oral administration of 1 mg/kg of methylprednisolone. Continuous Ag challenge induced an initial (first hour) peak of histamine release followed by a lower level plateau of histamine release during the next 4 hours. The level of histamine release during the second to fifth hours was significantly higher at these sites of continuous Ag challenge than at the codeine- or intermittent Ag-challenge sites. Levels of both tryptase and PGD2 were increased after the first hour of Ag or codeine challenge, and tryptase decreased progressively thereafter at all sites. In corticosteroid-treated subjects, the persistent histamine release during the second to fifth hours of Ag challenge was significantly reduced. In contrast, corticosteroid therapy did not affect histamine release during the first hour of Ag challenge nor the release of PGD2 or tryptase at any time period. These findings suggest that basophils are the source of the persistent histamine release at sites of continuous in vivo Ag challenge, since such release (1) was unaccompanied by release of tryptase or PGD2 (released from mast cells but not basophils), (2) did not occur after codeine challenge that activates mast cells but not basophils, and (3) was inhibited by steroids that inhibit the accumulation and release of histamine from basophils but not mast cells.

Administration, Oral↗

PubMed1990

Determinants of in vivo histamine release in cutaneous allergic reactions in humans.

To determine host factors influencing the magnitude of mediator release during ongoing cutaneous allergic reactions in humans, we compared, in 22 subjects, the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release to (1) the in vitro reactivity and sensitivity of basophils to antigen for histamine release and (2) skin test sensitivity and reactivity to antigen, histamine, and codeine. There was no significant correlation between the first-hour and second- to fifth-hour histamine release. With a combination of basophil, antigen, histamine, and codeine skin sensitivity and reactivity, 64% to 75% of the magnitude of the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release could be accounted for. We conclude that antigen-induced in vivo allergic responses are a complex phenomenon dependent, in part, on antigen sensitivity, basophil and mast cell reactivity, and end organ responsiveness to mediators.

Adolescent↗

PubMed1990

Release of histamine and tryptase during continuous and interrupted cutaneous challenge with allergen in humans.

To help in understanding the patterns of in vivo mediator release in human allergic skin reactions, we have used a skin chamber model to challenge the denuded bases of skin blisters of 11 sensitive subjects with pollen antigens (Ags) and codeine (C), a mast cell degranulator. Challenges were performed either (1) continuously for 6 hours or (2) in an intermittent fashion that is, Ag or C for the first hour, buffer for the next 4 hours, and then Ag or C during the sixth hour. Fluids in the overlying chamber were assayed for levels of the mast cell components, histamine and tryptase. There was peak release of both histamine and tryptase during the first hour of Ag incubation (89 +/- 11 ng/ml and 1428 +/- 260 ng/ml, respectively). At continuous Ag-challenge sites, there was a plateau of histamine levels (8.0 to 9.5 ng/ml) during the next 4 hours, whereas tryptase levels decreased progressively to baseline levels. Challenge of continuous Ag-incubation sites with C, a mast cell activator, led to another peak release of both histamine and tryptase. At interrupted Ag-challenge sites, histamine levels decreased abruptly, and tryptase levels decreased progressively after the first hour. Rechallenge of such sites with Ag during the sixth hour induced a peak release of histamine but no increase in tryptase levels. Continuous challenge with C for up to 5 hours in other sites induced an initial peak histamine release without a subsequent plateau. However, such a plateau of histamine (but not tryptase) release occurred after an initial C challenge if Ag was subsequently incubated in a continuous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗