Intravenous immunoglobulin inhibits IgE production in human B lymphocytes.

BACKGROUND: Intravenous immunoglobulin (IVIG) is commonly used as both an immune-enhancing and immune-modulating agent. Treatment with high doses of IVIG diminishes IgE secretion in patients with severe steroid-dependent asthma. OBJECTIVE: We studied the action of IVIG on IgE production in highly purified B lymphocytes stimulated without additional T cells to determine the action of IVIG on B lymphocytes. METHODS: Human B cells were purified from tonsils, and T lymphocytes were removed by E-rosetting. B cells were cultured with IL-4 (400 U/mL) and anti-CD40 antibodies (1 microg/mL¿, with or without additional IVIG. Cell proliferation was determined by 3[H]-thymidine uptake, and supernatant IgE was determined by ELISA. Cell cycle analysis was performed by flow cytometry, and IgE transcripts were measured by in situ hybridization. RESULTS: IVIG (5 mg/mL) decreased B-cell proliferation in IL4/anti-CD40-stimulated B cells by an average of 74% (+/-6%). Addition of IVIG up to 48 hours after initiation of cell culture led to significant diminution of cell proliferation at 96 to 120 hours. This effect was dose dependent, with 10 mg/mL being the most effective and doses under 0.1 mg/mL having minimal effect. IVIG diminished the number of stimulated cells progressing in the cell cycle by 30%, and there was no difference in cell viability between IVIG-treated and IVIG-untreated cells. The production of IgE in culture by anti-CD40/IL4-stimulated B lymphocytes was curtailed by greater than 80% after addition of 5 mg/mL IVIG. This was associated with a decrease in IgE (epsilon) transcripts in IVIG-treated cultures. CONCLUSION: These data indicate that diminution of IgE production in anti-CD40/IL-4-stimulated B cells by IVIG is due to inhibition of early events related to proliferation and progression in the cell cycle.

Immunotherapy for childhood asthma: is there a rationale for its use?

OBJECTIVE: This paper reviews the literature regarding immunotherapy in the management of childhood asthma. Immunotherapy is a well established treatment of venom allergy and allergic rhinitis, however its use in asthma remains controversial. DATA SOURCES: We reviewed the pediatric literature from 1966 to 1994 and evaluated the existing studies for clinical efficacy of immunotherapy in childhood asthma. STUDY SELECTION: Only 12 purely pediatric studies existed over the time period that we reviewed. The studies used a variety of different antigens including house dust, house dust mite, grass, mold, cat, dog, and combinations of antigens. RESULTS: In reviewing the studies, we assessed study duration, number of subjects, whether it was blinded, placebo controlled or open labeled, the measures of clinical efficacy and the assessments of specific and nonspecific bronchial reactivity. The studies were very heterogeneous, and therefore direct comparison and extrapolation of conclusions was difficult. The majority of the studies demonstrated either an improvement in asthmatic symptoms or a decrease in bronchial reactivity to the specific antigen employed, or both. The minority of studies demonstrated no clinical efficacy. The most consistent evidence of benefit was suggested in those trials employing house dust mite therapy, while immunotherapy for grass and cats demonstrated some benefit but the number of studies employing these treatments was very small. There are no trials that provide convincing evidence that immunotherapy with dog and mold antigens is effective for childhood reactive airway disease. CONCLUSION: Asthma is a multifactorial disease with many triggers. In establishing a role for immunotherapy one must consider all the different aspects such as allergic triggers, environmental stresses, and viral infections. The literature is unclear as to when immunotherapy should be initiated for childhood asthma. While there are suggestions that immunotherapy should be considered for the child with mild or moderate asthma and dust mite sensitivity when pharmacotherapy is not efficacious, the immunomodulatory properties of immunotherapy may actually be more tailored for early intervention in asthma rather than for use once symptoms have occurred. More research is required in order to clarify whether immunotherapy should be recommended more often for the treatment of childhood asthma.

Case report: milk-alkali syndrome and pancreatitis.

The relation between hypercalcemia and pancreatitis, first described in patients with hyperparathyroidism, is controversial. Other causes of hypercalcemia also have been associated with pancreatitis. In this report, the authors describe a patient with pancreatitis and the milk-alkali syndrome who had the classic triad of hypercalcemia, alkalosis, and renal insufficiency. The authors also review the literature for all the reported cases of pancreatitis associated with hypercalcemia.

Laparoscopic cholecystectomy: a treatment option for gallbladder disease in children.

Laparoscopic cholecystectomy was performed safely in two children ages 7 and 15 years. Special considerations were required in the younger child because of the discrepancy between the length of the instruments and the size of the peritoneal cavity. Both children remained in hospital less than 24 hours and were able to resume normal diet and activity quickly. Pediatric surgeons with special training in laparoscopic surgery may want to use this treatment modality for children with biliary tract disease.