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82. Neutrophil chemotaxis in flunisolide aerosol-treated asthmatic patients
2
American
Academy
of Aiiergy
Bone resorption was elevated in all patients. Bone formation was depressed in those receiving daily corticosteroids and greater than 20 mg of prednisone on alternate days but not in patients on lower doses of alternate-day predmsone. d41temate patients (total number, 23) were given sodium fluoride, cakium carbonate, and vitamin D supplements; but adminisiration of fluoride in an enteric-coated form initially failed to produce a rise in serum fluoride which suggests poor absorption. §odium fluoride, 7.5 mg daily, administered in a nonenteric-coated form caused a prompt rise in serum fluotide; with calcium and vitamin D bone formation rose to the normal range, but bone resorption remained elevated as demonstrated by annual bone biopsies in 9 patients. Qur results suggest that a combination of fluoride, calcium, and vitamin D will help prevent the osteoporosis that frequently accompanies corticosteroid administration.
unisolide aerosol treatment of nia! allergic rhinitis in children. S. Siegel, M.5., R. Katz, M.D., G. Racheiefsky, Calif. *, and S. Crepea, M.D., Los Angeles, In a double-blind, placebo-controlled study the efficacy and effects on adrenal function of flunisolide aerosol (FA) was evaluated in 53 atopic children with severe perennial allergic rhinitis. Their ages ranged from 5 to 16 yr. The patients were randomly assigned to either the active (FA, 27 patients) or pla.cebo (vehicle) group (26 patients). After a baseline period of 2 wk the patients received 2 sprays of FA 0.025% or placebo in each nostril twice daily for 12 wk. Response was assessed by daily symptom and medication scores, biweekly physical examinations, and patients’ and parents’ evaluations. Adrenal function was evaluated by measuring 3 successive daily resting cotiisol levels and an intravenous ACTH cortisol response test performed during the baseline period and after 12 wk of treatment. Statistical analysis of group differences were made. On FA the patients had significantly lower symptom and medication scores. Twenty-one (74%) of the FA group evaluated the response as being good to excellent in contrast to 2 (8%) in the placebo group. No evidence of adrenal suppression was noted in the resting cortisol levels or ACTH co&sol response tests. These data indicate that FA administered twice daily for a period of 12 wk is an effective agent for the treatment of perennial allergic rhinitis in children and does not suppress adrenal function.
ugmentation of IgE-mediated bistam~n@ release from human basophils by agocytic stimuli. Larry L. Thomas, Ph.D., and wrence
M. Lichtenstein,
M.D., Ph.D., Baltimore,
&like other granulocytes, the response of basophils to pbagocytic stimuli has not been characterized. We, there-
2. .ALEFlGY
CLIN. iMMuNoL. MARCH 197S
fore, examined the effect of phagocytic stimuli on the release of histamine from human basophils. The basophilcontaining mononuclear cell fraction was isolated from venous blood of allergic and nonallergic donors by Hypaque-Ficoll density centrifugation. Cells were incubated with phagocytic stimuli alone and in the presence of either appropriate antigen for allergic donors or anti-IgE serum for nonatopic individuals. Serum-treated zymosan particles (STZ) alone failed to stimulate histamine release (HR) (<2% to 3%) but regularly augmented both antigen-and anti-IgE-stimulated HR; the increment was 30% to 100% in most cases. Enhancement by STZ was present over the entire antigen concentration curves and was evident within 1 min after addition of stimuli. Zymosan (Z) not incubated with serum and Z incubated with serum containing 10 mill EDTA or with C3-deficient serum failed to augment FIR. Heat-aggregated human immunoglobulin similarly enhanced antigen-induced HR without stimulating HR alone. No augmentation was observed with donors who failed to release with anti-IgE or with immunologically desensitized cells. It is concluded that phagocytic stimuli do not cause histamine release alone but markedly augment IgEmediated release. This effect appears to involve previously described Fc receptors and a novel C3 receptor on basophils. Such an interaction in vivo may contribute to the initiation or exacerbation of allergic reactions.
80, Phagocytosis of immune cornp~~x@~ human eosinophils. David E. Normanseli, P and William
H. Grover,
Ph.D., Charlottesville,
Va.
Ingestion of immune complexes by eosinophils has been suggested for years but has not been conclusively proved. To approach this question, highly purified eosinophils were obtained by separating ieukocytes from anticoagulated and dextran-treated blood on a Hypaque gradient. Phagocytosis was assessed by incubation of eosinophils with latex particles coated with ragweed plus ragweed-allergic serum. Internalization of the particles was verified by electronmicroscopy analysis. In 3 1 of 33 experiments, eosinophils from normal donors ingested the coated particles but not uncoated particles nor particles coated with either allergen or serum alone. Ingestion was also seen when the particles were coated with other allergens plus specific allergic serum. The component of allergic serum which mediated the ingestion eluted with the IgG fraction on G-200 Sephadex and diethylaminoethyl cellulose chromatography, but it did not correlate with the ragweed radioallergosorbent test assay or the total IgE level of the serum nor with the skin reactivity of the serum donor and was unaffected by heating to 56’ C for 20 min. These data indicate that phagocytosis of coated latex particles by eosinophils is mediated by IgG antibody, not IgE, and that eosinophils may modulate immediate hypersensitivity reactions by an antibody-dependent antigen-clearing mechanism.
American
Academy
of Aiiergy
Bone resorption was elevated in all patients. Bone formation was depressed in those receiving daily corticosteroids and greater than 20 mg of prednisone on alternate days but not in patients on lower doses of alternate-day predmsone. d41temate patients (total number, 23) were given sodium fluoride, cakium carbonate, and vitamin D supplements; but adminisiration of fluoride in an enteric-coated form initially failed to produce a rise in serum fluoride which suggests poor absorption. §odium fluoride, 7.5 mg daily, administered in a nonenteric-coated form caused a prompt rise in serum fluotide; with calcium and vitamin D bone formation rose to the normal range, but bone resorption remained elevated as demonstrated by annual bone biopsies in 9 patients. Qur results suggest that a combination of fluoride, calcium, and vitamin D will help prevent the osteoporosis that frequently accompanies corticosteroid administration.
unisolide aerosol treatment of nia! allergic rhinitis in children. S. Siegel, M.5., R. Katz, M.D., G. Racheiefsky, Calif. *, and S. Crepea, M.D., Los Angeles, In a double-blind, placebo-controlled study the efficacy and effects on adrenal function of flunisolide aerosol (FA) was evaluated in 53 atopic children with severe perennial allergic rhinitis. Their ages ranged from 5 to 16 yr. The patients were randomly assigned to either the active (FA, 27 patients) or pla.cebo (vehicle) group (26 patients). After a baseline period of 2 wk the patients received 2 sprays of FA 0.025% or placebo in each nostril twice daily for 12 wk. Response was assessed by daily symptom and medication scores, biweekly physical examinations, and patients’ and parents’ evaluations. Adrenal function was evaluated by measuring 3 successive daily resting cotiisol levels and an intravenous ACTH cortisol response test performed during the baseline period and after 12 wk of treatment. Statistical analysis of group differences were made. On FA the patients had significantly lower symptom and medication scores. Twenty-one (74%) of the FA group evaluated the response as being good to excellent in contrast to 2 (8%) in the placebo group. No evidence of adrenal suppression was noted in the resting cortisol levels or ACTH co&sol response tests. These data indicate that FA administered twice daily for a period of 12 wk is an effective agent for the treatment of perennial allergic rhinitis in children and does not suppress adrenal function.
ugmentation of IgE-mediated bistam~n@ release from human basophils by agocytic stimuli. Larry L. Thomas, Ph.D., and wrence
M. Lichtenstein,
M.D., Ph.D., Baltimore,
&like other granulocytes, the response of basophils to pbagocytic stimuli has not been characterized. We, there-
2. .ALEFlGY
CLIN. iMMuNoL. MARCH 197S
fore, examined the effect of phagocytic stimuli on the release of histamine from human basophils. The basophilcontaining mononuclear cell fraction was isolated from venous blood of allergic and nonallergic donors by Hypaque-Ficoll density centrifugation. Cells were incubated with phagocytic stimuli alone and in the presence of either appropriate antigen for allergic donors or anti-IgE serum for nonatopic individuals. Serum-treated zymosan particles (STZ) alone failed to stimulate histamine release (HR) (<2% to 3%) but regularly augmented both antigen-and anti-IgE-stimulated HR; the increment was 30% to 100% in most cases. Enhancement by STZ was present over the entire antigen concentration curves and was evident within 1 min after addition of stimuli. Zymosan (Z) not incubated with serum and Z incubated with serum containing 10 mill EDTA or with C3-deficient serum failed to augment FIR. Heat-aggregated human immunoglobulin similarly enhanced antigen-induced HR without stimulating HR alone. No augmentation was observed with donors who failed to release with anti-IgE or with immunologically desensitized cells. It is concluded that phagocytic stimuli do not cause histamine release alone but markedly augment IgEmediated release. This effect appears to involve previously described Fc receptors and a novel C3 receptor on basophils. Such an interaction in vivo may contribute to the initiation or exacerbation of allergic reactions.
80, Phagocytosis of immune cornp~~x@~ human eosinophils. David E. Normanseli, P and William
H. Grover,
Ph.D., Charlottesville,
Va.
Ingestion of immune complexes by eosinophils has been suggested for years but has not been conclusively proved. To approach this question, highly purified eosinophils were obtained by separating ieukocytes from anticoagulated and dextran-treated blood on a Hypaque gradient. Phagocytosis was assessed by incubation of eosinophils with latex particles coated with ragweed plus ragweed-allergic serum. Internalization of the particles was verified by electronmicroscopy analysis. In 3 1 of 33 experiments, eosinophils from normal donors ingested the coated particles but not uncoated particles nor particles coated with either allergen or serum alone. Ingestion was also seen when the particles were coated with other allergens plus specific allergic serum. The component of allergic serum which mediated the ingestion eluted with the IgG fraction on G-200 Sephadex and diethylaminoethyl cellulose chromatography, but it did not correlate with the ragweed radioallergosorbent test assay or the total IgE level of the serum nor with the skin reactivity of the serum donor and was unaffected by heating to 56’ C for 20 min. These data indicate that phagocytosis of coated latex particles by eosinophils is mediated by IgG antibody, not IgE, and that eosinophils may modulate immediate hypersensitivity reactions by an antibody-dependent antigen-clearing mechanism.