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B S Bochner

Publications and source records attributed to B S Bochner.

At least 55 records · Page 3Linked to original sources
PubMed1998

The role of adhesion molecules in allergic inflammation and their suitability as targets of antiallergic therapy.

Adhesion molecules on leukocytes and tissue-resident cells are now known to mediate steps of the allergic inflammation response. Blockade of adhesion pathways is being actively explored as a potential strategy to therapeutically manage allergic diseases. The various adhesion molecules and their counterligands are discussed with respect to evidence supporting their role in allergic inflammation and suitability as therapeutic targets.

Animals↗
PubMed1998

New concepts in the pathogenesis and treatment of allergic asthma.

This review delineates the currently accepted, multifaceted approach to the care of an asthmatic patient. Therapy is based on our improved understanding of the pathophysiology of this complex disease, in which IgE and mediators derived from many cells contribute to airway inflammation. The latest trends in therapy involve the institution of anti-inflammatory medications relatively early in disease. With the recent availability of a novel class of therapies, the leukotriene antagonists, and other therapies based on antagonism of adhesion molecules, cytokines, chemokines, or IgE itself, the future may provide additional alternatives for the physician treating patients with asthma.

Anti-Asthmatic Agents↗
PubMed1997

Cutaneous injection of RANTES causes eosinophil recruitment: comparison of nonallergic and allergic human subjects.

RANTES, a member of the C-C chemokine family, is a potent chemoattractant for T lymphocytes and eosinophils, but not neutrophils. To determine the effect of RANTES on cell recruitment in vivo, we injected up to 4 microg of RANTES intradermally into both allergic and nonallergic subjects and obtained biopsies 30 min, 6 h, and 24 h later. A dose- and time-dependent recruitment of eosinophils, CD45RO+ cells, and CD3+ cells was observed, with no effect seen on polymononuclear, cutaneous lymphocyte Ag+, CD68+, or tryptase+ cells. Eosinophil recruitment occurred more rapidly in allergic subjects than in nonallergic subjects. No eosinophil infiltrate was observed in nonallergic biopsies at 30 min and 6 h, whereas significant eosinophil recruitment was observed in allergic subjects by 30 min, reaching near-maximum levels by 6 h. The peak responses at 24 h were similar in both groups (nonallergic, 110 +/- 24 eosinophils/mm2; allergic, 113 +/- 38 eosinophils/mm2). The two groups had comparable numbers of circulating eosinophils. Major basic protein staining demonstrated eosinophil degranulation in both allergic and nonallergic groups. RANTES injection resulted in activation of endothelial E-selectin expression at 24 h. Incubation of cultured HUVECs with RANTES had no effect on adhesion molecule expression, suggesting that the in vivo effect may have been indirect. Our studies demonstrate that RANTES is a potent chemoattractant for eosinophils, CD3+ cells, and CD45RO+ cells in human skin. The accelerated eosinophil recruitment in allergic subjects provides support for the hypothesis that eosinophils from these subjects are primed in vivo.

Administration, Cutaneous↗
PubMed1997

P- and L-selectin mediate distinct but overlapping functions in endotoxin-induced leukocyte-endothelial interactions in the rat mesenteric microcirculation.

Endotoxin is a potent stimulus of leukocyte infiltration, but the adhesion-related mechanisms responsible for LPS-induced cell recruitment events in vivo remain poorly characterized. Utilizing intravital microscopy, we examined the role of P- and L-selectin in LPS-induced inflammation. We demonstrated that superfusion of rat mesentery with LPS resulted in significant increases in both leukocyte rolling and adherence, which were maintained for at least 2 h. Pretreatment with a P-selectin neutralizing mAb only partially inhibited LPS-induced leukocyte rolling, but completely inhibited LPS-induced leukocyte adherence throughout the 2-h observation period. Pretreatment with an L-selectin neutralizing mAb dramatically inhibited LPS-induced increases in leukocyte rolling, but unlike the P-selectin mAb did not inhibit leukocyte adhesion. Fucoidin, which blocks both P- and L-selectin function, completely inhibited LPS-induced leukocyte rolling and adhesion. Consistent with previous studies, leukocyte rolling velocities on P-selectin were observed to be far less than velocities observed for leukocytes rolling on L-selectin in vivo. These data suggest that P-selectin plays a role in LPS-induced rolling and is essential for LPS-induced leukocyte adherence, while L-selectin functions in LPS-induced rolling, but not in adhesion.

Animals↗
PubMed1997

Antibody to VLA-4, but not to L-selectin, protects neuronal M2 muscarinic receptors in antigen-challenged guinea pig airways.

Antigen challenge of sensitized guinea pigs decreases the function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lung, potentiating vagally induced bronchoconstriction. Loss of M2 receptor function is associated with the accumulation of eosinophils around airway nerves. To determine whether recruitment of eosinophils via expression of VLA-4 and L-selectin is critical for loss of M2 receptor function, guinea pigs were pretreated with monoclonal antibodies to VLA-4 (HP1/2) or L-selectin (LAM1-116). Guinea pigs were sensitized and challenged with ovalbumin, and M2 receptor function was tested. In controls, blockade of neuronal M2 muscarinic receptors by gallamine potentiated vagally induced bronchoconstriction, while in challenged animals this effect was markedly reduced, confirming M2 receptor dysfunction. Pretreatment with HP1/2, but not with LAM1-116, protected M2 receptor function in the antigen-challenged animals. HP1/2 also inhibited the development of hyperresponsiveness, and selectively inhibited accumulation of eosinophils in the lungs as measured by lavage and histology. Thus, inhibition of eosinophil influx into the lungs protects the function of M2 muscarinic receptors, and in so doing, prevents hyperresponsiveness in antigen-challenged guinea pigs.

Animals↗
PubMed1997

Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines.

Monocyte chemotactic protein-4 (MCP-4) is a newly identified C-C chemokine with potent eosinophil chemoattractant properties. We describe studies of its biological activity in vitro to induce chemotaxis of peripheral blood eosinophils and to induce histamine release from IL-3-primed peripheral blood basophils. MCP-4 and eotaxin caused a similar rise in eosinophil intracytoplasmic Ca2+ and complete cross-desensitization. MCP-4 also abolished the eosinophil Ca2+ response to MCP-3 and partially desensitized the response to macrophage inflammatory protein-1alpha. MCP-4 activated cell migration via either CCR2b or CCR3 in mouse lymphoma cells transfected with these chemokine receptors. MCP-4 inhibited binding of 125I-eotaxin to eosinophils and CCR3-transfected cells and inhibited 125I-MCP-1 binding to CCR2b-transfectants. MCP-4 mRNA was found in cells collected in bronchoalveolar lavage of asthmatic and nonasthmatic subjects and was prominently expressed in human lung and heart. MCP-4 mRNA was expressed in several human bronchial epithelial cell lines after cytokine stimulation. Pretreatment of BEAS-2B epithelial cells with the glucocorticoid budesonide inhibited MCP-4 mRNA expression. These features make MCP-4 a candidate for playing a role in eosinophil recruitment during allergic respiratory diseases.

Amino Acid Sequence↗
PubMed1997

Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody.

Treatment of allergic disease by decreasing circulating IgE with anti-IgE Abs is currently under clinical study. Based on previous unrelated studies, it appeared likely that Fc(epsilon)RI expression on basophils and mast cells might also be regulated by levels of circulating IgE Ab. Therefore, the expression of IgE and Fc(epsilon)RI on human basophils was examined in 15 subjects receiving humanized anti-IgE mAb intravenously. Treatment with the anti-IgE mAb decreased free IgE levels to 1% of pretreatment levels and also resulted in a marked down-regulation of Fc(epsilon)RI on basophils. Median pretreatment densities of Fc(epsilon)RI were approximately 220,000 receptors per basophil and after 3 mo of treatment, the densities had decreased to a median of 8,300 receptors per basophil. Flow cytometric studies, conducted in parallel, showed similar results and also showed in a subset of 3 donors that receptors decreased with a t1/2 of approximately 3 days. The responsiveness of the cells to IgE-mediated stimulation using anti-IgE Ab was marginally decreased (approximately 40%) while the response of the same cells to stimulation with dust mite Ag, Dermatophagoides farinae, was reduced by approximately 90%. One possible explanation for these results is that Fc(epsilon)RI density is directly or indirectly regulated by plasma-free IgE levels.

Adult↗
PubMed1997

Studies of cell adhesion and flow cytometric analyses of degranulation, surface phenotype, and viability using human eosinophils, basophils, and mast cells.

Products derived from eosinophils, basophils, and mast cells are considered critical to the development of allergic diseases. Studies of the selective recruitment, accumulation, and/or activation of these cells during human allergic inflammatory reactions in vitro and in vivo have been facilitated by a wide variety of methods. Some have been developed to identify and isolate these cells from a variety of sites, including blood, airway secretions, and surgical or autopsy tissues. Once enriched in purity, assays of cell adhesion to endothelium, epithelium, matrix proteins, and purified, immobilized counterligands for integrins, selectins, or immunoglobulin gene superfamily structures can be performed in vitro under both static and flow conditions. Techniques involving flow cytometry, utilizing characteristics of cellular light scatter and immunofluorescence, have permitted the elucidation of cell surface phenotype and have aided in quantification of cellular degranulation and viability. These approaches have yielded new information on the function of human eosinophils, basophils, and mast cells and have suggested unique cell-specific pathways of cell recruitment, activation, and survival that may contribute to the pathogenesis of allergic diseases.

Antigens, Surface↗
PubMed1997

Regulation of alpha 4 integrin-mediated adhesion of human eosinophils to fibronectin and vascular cell adhesion molecule-1.

BACKGROUND: Eosinophils selectively accumulate at sites of allergic inflammation. Their recruitment is dependent on both the expression and functional activity of cell adhesion molecules. How the functional activity of cell adhesion molecules on eosinophils is regulated is poorly understood. OBJECTIVE: Our objective was to examine the functional activity of alpha 4 integrins on human eosinophils and its regulation by various agents. METHODS: Function of alpha 4 integrins on human eosinophils was examined by testing adhesion to immobilized fibronection and vascular cell adhesion molecule-1 (VCAM-1) in the presence or absence of a monoclonal antibody (mAb) (8A2) that activates beta 1 integrin function. RESULTS: Spontaneous eosinophil adhesion to VCAM-1 was enhanced by 8A2, but adhesion to fibronectin could only be detected in the presence of 8A2. Concentrations of 8A2 that were approximately 100-fold less than saturating induced maximal eosinophil adhesion. Adhesion to VCAM-1 in the presence of 8A2 was effectively inhibited by alpha 4 and beta 1 integrin mAbs: beta 7 mAb had partial inhibitory activity. Connecting segment-1 peptide and alpha 4 mAb blocked 8A2-dependent fibronectin binding: beta 1, beta 2, and beta 7 integrin mAbs had partial inhibitory activity. Eosinophils obtained from bronchoalveolar lavage fluids and blood eosinophils stimulated with IL-5, platelet-activating factor, or RANTES displayed increased beta 2 integrin-dependent, not alpha 4 integrin-dependent, attachment. Spontaneous adhesion of eosinophils to VCAM-1 was significantly reduced by the tyrosine kinase inhibitor tyrphostin B46 (inhibitory concentration of 50% approximately equal to 20 mumol/L); this effect was reversed by 8A2. CONCLUSIONS: The functional activity of integrins on eosinophils can be positively and negatively regulated. Altered integrin avidity may influence eosinophil recruitment in vivo.

Antibodies, Monoclonal↗
PubMed1997

Phenotypic analysis of alveolar macrophages and monocytes in allergic airway inflammation. I. Evidence for activation of alveolar macrophages, but not peripheral blood monocytes, in subjects with allergic rhinitis and asthma.

Macrophages and monocytes play important proinflammatory roles in allergic inflammation. We hypothesized that these cells would express an activated phenotype in allergic disease of the airways. We therefore compared the expression of 17 activation markers on the surface of alveolar macrophages (AM) and peripheral blood monocytes (PBM) in 13 subjects with asymptomatic allergic asthma (AA), nine subjects with asymptomatic allergic rhinitis (AR), and 11 nonallergic (N). AM were obtained by BAL, and PBM were simultaneously obtained by phlebotomy; both were analyzed for expression of surface markers using a new two-color flow cytometry method that essentially eliminates background autofluorescence. The proportions of AM in BAL fluid from AA, AR, and N subjects were 84 +/- 2, 85 +/- 4, and 91 +/- 1%, respectively; viability always exceeded 92%. Expression of eight markers (CD16, CD18, CD32, CD44, CD71, HLA Class I, HLA DR, and HLA DQ) was significantly (p < 0.05) higher on AM of AA than on N; expression of six markers (CD11a, CD16, CD18, CD71, HLA Class I, and HLA DR) was higher on AM of AR than on N, with differences in CD44 levels approaching statistical significance (p = 0.07). Expression of one marker, CD44, was significantly higher on AM of AA than on those of AR, with differences in HLA Class I levels approaching statistical significance (p = 0.07). In contrast, no significant differences were found among the three groups in the expression in eight other markers (CD11b, CD14, CD23, CD29, CD33, CD35, CD63, and CD64). Finally, similar analysis of PBM from these same subjects failed to find any difference between the three groups in any of the 17 activation markers studied. These data suggest that AM are activated in allergic respiratory diseases, and that levels of HLA Class I and CD44 on AM are altered during allergic inflammation in the upper and lower airways.

Adult↗
PubMed1997

Phenotyping and cytokine regulation of the BEAS-2B human bronchial epithelial cell: demonstration of inducible expression of the adhesion molecules VCAM-1 and ICAM-1.

Airway epithelium may actively participate in inflammatory responses, such as occur in asthma. The presence and regulation of surface molecules on the airway epithelium, however, is incompletely understood. We have determined the phenotype of the human bronchial epithelial cell line BEAS-2B by flow cytometry. We confirmed previous observations that human bronchial epithelial cells constitutively express CD29, CD44, CD49a, CD49b, CD49c, CD49d, CD49e, CD49f, CD51, CD54 (ICAM-1), CD61, and HLA class 1. BEAS-2B cells were also found to constitutively express CD9, CD13, CD15, CD15s, CD23, CD33, CD36, CD40, CD41b, CD42b, CD48, CD50, CD71, and CD102 (ICAM-2). Culture of BEAS-2B cells with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta (1 ng/ml) was found to enhance intercellular adhesion molecule-1 (ICAM-1) expression (several fold) and induce de novo CD106 [vascular cell adhesion molecule-1 (VCAM-1)] expression. TNF-alpha or IL-1beta did not change the expression of CD9, CD13, CD16, CD23, CD29, CD31, CD32, CD35, CD45, CD61, or CD64 in BEAS-2B cells. IL-4 (1 ng/ml) also induced expression of VCAM-1 (1.5-fold) but not ICAM- expression while interferon-gamma (1 ng/ml) enhanced only ICAM-1 expression (2-fold). Maximal VCAM-1 expression was obtained with the combination of TNF-alpha and IL-4 (8-fold). Using Northern blot hybridization analysis, ICAM-1 and VCAM-1 mRNA was detected in BEAS-2B cells stimulated with cytokines. VCAM-1 on stimulated BEAS-2B was functionally active as determined by adhesion of purified eosinophils and blockade with specific antibodies. Primary isolates of bronchial epithelial cells produced detectable levels of VCAM-1 protein and mRNA as detected by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. These results suggest that cytokine activation induces expression of ICAM-1 and VCAM-1 on airway epithelium, an event which may influence leukocyte infiltration and activation.

Antigens, CD↗
PubMed1997

Expression and function of beta 1 integrins on human eosinophils.

Eosinophils preferentially accumulate at sites of chronic allergic diseases such as bronchial asthma. The mechanisms by which selective eosinophil migration occurs are not fully understood. However, interactions of cell-surface adhesion molecules on the eosinophil with molecular counterligands on endothelial and epithelial cells, and on extracellular matrix proteins, are likely to be critical during the recruitment process. One possible mechanism for selective eosinophil recruitment involves the alpha-4-beta-1 (VLA-4) integrin which is not expressed on neutrophils. Correlations have been found between infiltration of eosinophils and endothelial expression of VCAM-1, the ligand for VLA-4, in the lungs of asthmatic individuals as well as in late phase reactions in the lungs, nose and skin. Epithelial and endothelial cells respond to the Th2-type cytokines IL-13 with selective de novo expression of VCAM-1, consistent with the possible role of VCAM-1/VLA-4 interactions in eosinophil influx during allergic inflammation. Both beta-1 and beta-2 integrins on eosinophils exist in a state of partial activation. For example, eosinophils can be maximally activated for adhesion to VCAM-1 or fibronectin after exposure to beta-1 integrin-activating antibodies or divalent cations, conditions that do not necessarily affect the total cell surface expression of beta-1 integrins. In contrast, cytokines like IL-5 prevent beta-1 integrin activation while promoting beta-2 integrin function. Furthermore, ligation of integrins can regulate the effector functions of the cell. For example, eosinophil adhesion via beta-1 and/or beta-2 integrins has been shown to alter a variety of functional responses including degranulation and apoptosis. Thus, integrins appear to be important in mediating eosinophil migration and activation in allergic inflammation. Strategies that interfere with these processes may prove to be useful for treatment of allergic diseases.

Asthma↗
PubMed1997

Cysteinyl leukotrienes induce P-selectin expression in human endothelial cells via a non-CysLT1 receptor-mediated mechanism.

Cysteinyl leukotrienes are bioactive lipid mediators known to possess potent proinflammatory actions. Included in these are effects on vascular endothelium to promote surface expression of the adhesion molecule P-selectin. In the present study we were interested in investigating the receptor mechanism(s) involved in cysteinyl leukotriene-induced endothelial P-selectin expression. As such we examined the effect of several potent and selective cysteinyl leukotriene receptor antagonists on this response. Incubation of cultured human umbilical vein endothelial cells (HUVEC) with the cysteinyl leukotrienes leukotriene C4 (LTC4) or leukotriene D4 (LTD4) induced surface expression of P-selectin which was concentration dependent and rapid in onset. Expression of endothelial P-selectin induced by either LTC4 or LTD4 was not blocked however by pretreatment of HUVEC with the selective cysteinyl leukotriene-1 (CysLT1) receptor antagonists SKF 104353, pranlukast or zafirlukast before agonist exposure. In contrast, SKF 104353 effectively antagonized the LTC4-induced contractions in isolated human bronchial smooth muscle preparations, shifting the agonist dose-response curve to the right by some 3 log-fold in this tissue. The present results suggest that cysteinyl leukotrienes induce surface expression of endothelial P-selectin via a mechanism independent of the CysLT1 receptor.

Cells, Cultured↗
PubMed1996

Counter-receptors on human basophils for endothelial cell adhesion molecules.

Ligands on human basophils for the endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), and E-selectin were investigated. Adhesion of basophils to endothelial cells was inhibited by mAb recognizing CD18, CD11a, and/or CD11b, with the pattern and magnitude of inhibition dependent upon the activation state of the basophils and endothelium. Adhesion to recombinant VCAM-1 was completely inhibited by mAb recognizing alpha 4 integrin and partially by mAb to the beta 1 or beta 7 subunit; surface expression of these integrins was also detected. Adhesion to recombinant MAdCAM-1 expressed on Chinese hamster ovary cells was completely inhibited by mAb recognizing alpha 4 and/or beta 7 integrins. Adhesion to recombinant E-selectin was completely inhibited by basophil pretreatment with neuraminidase and partially inhibited by endo-beta-galactosidase. By flow cytometry, bimodal patterns of expression of sialyl-Lewis X- and sialyl-dimeric-Lewis X were observed, and adherent cells tended to be sialyl-dimeric-Lewis X positive. Thus, basophils express beta 1, beta 2, and beta 7 integrins along with sialylated surface ligands that may interact with the endothelium during basophil recruitment responses.

Animals↗
PubMed1996

Hydrogen peroxide and superoxide modulate leukocyte adhesion molecule expression and leukocyte endothelial adhesion.

While endothelial oxidant generation and subsequent leukocyte chemotaxis and activation are important mechanisms of tissue damage in ischemic organs, it is not known if oxidant generation may be involved in triggering the subsequent leukocyte-mediated injury which occurs. Questions remain whether particular oxidants and oxygen-free radicals are capable of modulating the expression of leukocyte adhesion molecules and effecting leukocyte endothelial adhesion. Studies were performed to determine the effect of different biologically occurring oxidant molecules and oxygen free radicals including: .O2-, .OH, and H2O2 on the expression of integrin and selectin adhesion molecules on the surface of human PMNs and to determine the effect of these alterations on PMN adhesion to the endothelium. Adhesion molecule expression on the surface of human PMNs was measured by immunofluorescence flow cytometry. Electron paramagnetic resonance spectroscopy was applied to characterize the presence of exogenous free radical generation as well as that from activated PMNs. It was observed that these oxidants can cause up-regulation of CD11b and CD18 expression with shedding of L-selectin. The kinetics and dose-response of these effects were analyzed and their functional significance determined by measuring PMN adhesion to cultured human aortic endothelial monolayers. These studies demonstrate that oxygen free radicals and non-radical oxidants can directly trigger PMN activation and adhesion to vascular endothelium.

Antigens, CD↗
PubMed1996

Detection of the chemokine RANTES and endothelial adhesion molecules in nasal polyps.

BACKGROUND: To better understand the mechanisms of eosinophil recruitment into the upper airways, we examined human nasal polyps for the expression of the chemotactic cytokine RANTES and the endothelial adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1). METHODS: Routine histologic examination and immunostaining with antibodies to RANTES, E-selectin, and VCAM-1 were performed on three types of tissues: nasal polyps, sinus mucosa, or turbinates from patients undergoing other elective procedures (S/T), and nasal biopsy specimens from nonallergic volunteers (NA). To further quantify the expression of endothelial adhesion molecules, some tissue samples were homogenized, and the resulting supernatants were assayed with sandwich ELISAs for VCAM-1 and E-selectin. RESULTS: Polyp eosinophil counts ranged from 19/mm2 to 1818/mm2 (763 +/- 120/mm2, mean +/- SEM) and were significantly higher than those found in the control tissues (5 +/- 2 in S/T samples and 20 +/- 9 in NA samples, p < 0.002). Immunochemical staining for RANTES was observed in 11 of 14 polyps; intense staining for RANTES (grade 3) was observed in six of 14 polyps. None of nine S/T samples or five NA samples demonstrated grade 3 staining. Staining with anti-RANTES was largely localized to airway and glandular epithelium. There was no significant correlation between counts of eosinophils or the combined total of eosinophils plus mononuclear cells and the intensity of epithelial RANTES staining in all nasal tissues. Staining for VCAM-1, as well as for E-selectin, was detected in 11 of 14 polyps and eight of 13 control tissues. VCAM-1 detected by ELISA in polyp tissues (6.8 +/- 1.3 micrograms/gm) was higher than that found in six S/T samples (1.2 +/- 0.3 micrograms/gm, p < 0.005) and in two NA samples (1.8 +/- 0.02 micrograms/gm, p = 0.08). E-selectin values in polyps (1.4 +/- 0.3 micrograms/gm) were not statistically different from those detected in six S/T samples (0.5 +/- 0.2 microgram/gm) or two NA samples (1.6 +/- 0.4 microgram/gm). Counts of eosinophils and eosinophils plus mononuclear cells displayed a strong correlation with VCAM-1 ELISA values (p < 0.005 and p < 0.004, respectively) but not with VCAM-1 staining. VCAM-1 staining correlated with EG2-positive eosinophils in nasal polyp tissues (p < 0.01). E-selectin staining did not correlate with either neutrophil or eosinophil counts. CONCLUSIONS: These studies demonstrate that the chemokine RANTES is produced in vivo predominantly to nasal epithelium. Endothelial activation, as indicated by adhesion molecule expression, occurs in human nasal polyp tissues and in control tissues, possibly reflecting the continued antigen exposure of the nasal mucosa. The correlations found in this study suggest that expression of VCAM-1 plays a role in the selective recruitment of eosinophils and mononuclear cells into nasal polyp tissues and that RANTES may be more important in localizing eosinophils to the epithelium.

Adult↗
PubMed1996

Glucocorticosteroid inhibition of cytokine production: relevance to antiallergic actions.

We believe that there are the following four classes of glucocorticoid-sensitive cytokines that are involved in cell recruitment: (1) those that activate endothelium nonspecifically; (2) those that activate endothelium specifically; (3) those that activate, prime, and prolong the survival of eosinophils; and (4) those that stimulate movement of cells up into the epithelium. Glucocorticoids inhibit the generation of these cytokines and thereby prevent several different aspects of inflammation, including the activation and recruitment of inflammatory cells (eosinophils, basophils, and lymphocytes) and the release of inflammatory mediators. We believe such pleiotropic actions account for the efficacy and widespread use of glucocorticoids in the treatment of asthma.

Anti-Allergic Agents↗