Effects of Corticosteroids and Splenectomy on the Immune Clearance and Destruction of Erythrocytes

Atkinson, John P.; Schreiber, Alan D.; Frank, Michael M.

doi:10.1172/jci107325

Cited by 104 publications

(46 citation statements)

References 17 publications

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“…4). Also, as shown in earlier studies, corticosteroids decreased splenic sequestration of IgG-coated cells without altering splenic weight (15). Sensitized cells were cleared in cortisone-treated animals as if they had fewer sensitizing sites per cell.…”

Section: Methodssupporting

confidence: 76%

“…One action of corticosteroids is to decrease the metabolic activity and function of macrophages (15,16). It was of interest, therefore, to determine whether stimulation of the RES would alter erythrocyte clearance.…”

Section: The Journal Of Clinical Investigation Volume 53 June 1974-17mentioning

confidence: 99%

“…This experimental model also permitted quantitative assessment of the effects of various therapeutic modalities on the destruction of the antibody-sensitized erythrocytes. Thus, corticosteroid therapy reduced clearance of IgGand IgM-sensitized cells, while splenectomy only influenced the clearance of IgG-sensitized cells (15). In these cases the distinctive pattern of clearance remained unchanged with therapy, but sensitized erythrocytes were cleared as if they had fewer antibody molecules per cell.…”

Section: Introductionmentioning

confidence: 96%

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The Effect of Bacillus Calmette-Guerin-Induced Macrophage Activation on the In Vivo Clearance of Sensitized Erythrocytes

Atkinson¹,

Frank²

1974

J. Clin. Invest.

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A B S T R A C T The clearance of 5'Cr-labeled guinea pig erythrocytes, sensitized with a known amount of IgM or IgG antibody, was examined in normal and BCGinfected guinea pigs. In normal animals, IgM-coated cells were rapidly sequestered in the liver. Most of these cells were then slowly released into the circulation where they survived normally as Coombs-positive erythrocytes. Neither the site nor extent of initial clearance showed major alterations in BCG-infected animals; however, there was no return of the sequestered erythrocytes into the circulation. This pattern of clearance was only seen in normals at very high levels of sensitization. In contrast to the IgM studies, the pattern of clearance of IgGsensitized erythrocytes was not altered, but the rate and magnitude was markedly increased at all levels of sensitization. In addition, complement-independent clearance of IgG-sensitized erythrocytes was augmented in BCGinfected guinea pigs lacking classical complement pathway function. The spleen remained the organ primarily responsible for this increased clearance of IgG-sensitized erythrocytes. Sensitized cells in BCG-infected animals were removed from the circulation as if they were coated with several times the amount of antibody. Serum factors were shown not to be responsible for the increased clearance. These data suggest that increased macrophage activation in BCG-infected animals plays a critical role in determining the consequences of cell sensitization in vivo. These studies may help to explain exacerbations of hemolytic anemias and related states after intercurrent infections.

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Section: Methodssupporting

confidence: 76%

Section: The Journal Of Clinical Investigation Volume 53 June 1974-17mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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The Effect of Bacillus Calmette-Guerin-Induced Macrophage Activation on the In Vivo Clearance of Sensitized Erythrocytes

Atkinson¹,

Frank²

1974

J. Clin. Invest.

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“…Fcy receptor-mediated binding and phagocytosis of IgGsensitized erythrocytes (EA) by monocytes in vitro were significantly enhanced 24 hours after the final dose of pulse IVMP (pre-IVMP versus post-IVMP 43 f 14% versus 53 f 12% EA rosettes, P < 0.01; 3.00 2 1.04 versus 3.99 & 1. 30 EA ingested/monocyte, P < 0.01). In contrast, there was no change in the phagocytosis of an Fcy receptor-independent probe, neuraminidasetreated erythrocytes.…”

Section: High-dose Pulse Intravenous Methylprednisolone Enhancesmentioning

confidence: 89%

High‐Dose, pulse intravenous methylprednisolone enhances fcγ receptor–mediated mononuclear phagocyte function in systemic lupus erythematosus

Salmon

Kapur

Meryhew

et al. 1989

Arthritis & Rheumatism

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The benefit of high-dose, pulse intravenous methylprednisolone (IVMP) for some patients with active lupus nephritis would appear paradoxical, since active nephritis is associated with profound abnormalities in Fcy receptor function, and several studies have demonstrated that glucocorticoids decrease monocyte Fc y receptor expression and phagocytic function. To resolve this paradox, we investigated the possibility that pulse IVMP might enhance monocyte Fcy receptor function in patients with systemic lupus erythematosus (SLE). Circulating immune complex (CIC) levels, Fcy receptor-mediated clearance, and Fc y receptor-dependent monocyte function were analyzed in 23 SLE patients before and after pulse IVMP (1 gm daily for 3 days). A biphasic response in CIC levels, determined by a staphylococcal protein A binding assay, was observed. Initially, CIC levels increased within 2-4 hours after the first dose of pulse IVMP and then decreased by 50% within 24-48 hours after the completion of therapy. Fcy

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“…Such alterations in membrane chemistry may affect blood-brain barrier permeability leading to the development of immune mediated CNS disease. High doses of corticosteroids impair the reticuloendothelial system clearance of immune complexes (6). These alterations of clearance kinetics may transiently predispose to the development of CNS manifestations.…”

mentioning

confidence: 99%

Central nervous system manifestations after pulse therapy for systemic lupus erythematosus

Ayoub

Torretti

Harrington

1983

Arthritis & Rheumatism

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We (1,2) and others (3) have shown that the slow calcium channel blocking agent nifedipine is effective in the treatment of Raynaud's phenomenon. Dr. JafFe's letter (4) prompts us to report our preliminary results of a single-blind study of nifedipine in the treatment of cutaneous ischemic ulceration in progressive systemic sclerosis.We report here the results of the first 4 patients included in this study (3 female and I male: mean age 54 years, range 42-68). These patients met the criteria for scleroderma in accordance with the preliminary criteria for the classification of systemic sclerosis (5) (mean duration of definite scleroderma: 5.5 years, range 3-8). All had typical Raynaud's phenomenon, with a mean duration of symptoms of 25.5 years, range 12-43. All had refractory digital ulcerations. Three patients had previously been treated with penicillamine, and 1 with penicillamipe and colchicine, without response. Three patients had previously been treated with various vasodilators without response. None of the patients was using other vasoactive medication during the study.After we had obtained their informed consent, patients were entered into a prospective study with a singleblind protocol. After 1 month of baseline assessment, the single-blind trial consisted of (a) placebo 4 times a day for 6 weeks and (b) nifedipine 20 mg 4 times a day for the final 6 weeks.At each weekly visit inquiries were made about any side effects related to treatment; cutaneous ischemic changes in the hands were recorded. Daily frequency of Raynaud's phenomenon was determined from a diary kept by the patient. The severity of digital vasospastic attacks was assessed by means of a 10 cm visual analog scale, with 0 representing minimum and 10 representing maximum severity. Drug effectiveness in the treatment of Raynaud's phenomenon was assessed by means of a similar 10 cm visual analog scale, with 0 representing no effect and 10 representing complete abolition of symptoms.The mean daily frequency of Raynaud's phenomenon was 8.7 (range 6.9-11.1) for the baseline period, 8.8 (range 6.1-10.6) for the placebo period, and 2.7 (range 2.3-3.1) for the nifedipine period of the study. The severity of digital vasospastic attacks was 8.8 (range 8.4-9.2) for the baseline peribd, 8.7 (rqnge 8.2-9.3) for the placebo period, and 2.1 (range 1.42.7) for the nifedipine period of the study. The patient score for drug effectiveness in Raynaud's phenomenon was 0.2 (range 0-0.9) for placebo and 6.9 (range 5.9-7.9) for nifedipine.The mean number of digital ulcerations was 7.25(range 6-10) at the end of the baseline period, 7.75 (range 6-10) at the end of the placebo period, and 0.5 (range 0-1) at the end of the nifedipine period of the study. At the end of the nifedipine period, all of the digital ulcers had completely healed in patients 1 and 2; 6 of the 7 digital ulcerations had completely healed in patient 3, and 5 of the 6 in patient 4. Side effects with nifedipine occurred in the 4 patients but were generally mild, and no patient discontinued the stud...

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Effects of Corticosteroids and Splenectomy on the Immune Clearance and Destruction of Erythrocytes

Abstract: A B S T R A C T Corticosteroids and splenectomy constitute two important therapeutic modalities in the treatment of autoimmune hemolytic anemia. Each

Cited by 104 publications

References 17 publications

The Effect of Bacillus Calmette-Guerin-Induced Macrophage Activation on the In Vivo Clearance of Sensitized Erythrocytes

The Effect of Bacillus Calmette-Guerin-Induced Macrophage Activation on the In Vivo Clearance of Sensitized Erythrocytes

High‐Dose, pulse intravenous methylprednisolone enhances fcγ receptor–mediated mononuclear phagocyte function in systemic lupus erythematosus

Central nervous system manifestations after pulse therapy for systemic lupus erythematosus

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