PMID- 21255135 OWN - NLM STAT- MEDLINE DCOM- 20120629 LR - 20110414 IS - 1365-2222 (Electronic) IS - 0954-7894 (Linking) VI - 41 IP - 5 DP - 2011 May TI - Intravenous immunoglobulin attenuates airway hyperresponsiveness in a murine model of allergic asthma. PG - 718-28 LID - 10.1111/j.1365-2222.2010.03663.x [doi] AB - BACKGROUND: Intravenous immunoglobulin (IVIG) has potent anti-inflammatory and immune-modulating properties. IVIG has been utilized as a steroid-sparing agent in severe asthma, but the results of clinical trials have been conflicting. OBJECTIVE: To determine whether IVIG is able to attenuate bronchial reactivity, pulmonary inflammation and T cell function using a murine model of allergic airways disease. METHODS: BALB/c or C57BL/6 mice were sensitized to ovalbumin (OVA) or a phosphate-buffered saline control using local nasal sensitization, and then received five intranasal challenges on days 28-32 before sacrifice. Mice were treated intraperitoneally with either IVIG (1-2 g/kg) or equivalent human serum albumin 24 h before the first OVA challenge. Bronchial reactivity to methacholine was examined using the FlexiVent small animal ventilator. We evaluated pulmonary histology, mRNA from lung digests for T-helper type 2 (Th2)-related genes and bronchoalveolar lavage for cell counts and cytokines. Splenocytes were utilized to study OVA-induced cell proliferation, cytokine production and dendritic cell maturation. RESULTS: IVIG markedly attenuated the perivascular and peribronchial pulmonary inflammation, and decreased bronchial hyperresponsiveness to methacholine. IVIG treatment of splenocytes from sensitized animals diminished cellular proliferation to OVA, whereas IVIG treatment in vivo markedly attenuated OVA-driven splenocyte proliferation. This is accompanied by diminished IL-13 and TNF-alpha levels in splenocyte culture, decreased expression of Jagged-1, increased Delta-4 and decreased GATA-3 mRNA levels, signs that IVIG has suppressed the expected Th2 response that accompanies repeated allergen exposure. Increased regulatory T cells were found in draining pulmonary lymph nodes in IVIG-treated mice but not in controls. CONCLUSIONS AND CLINICAL RELEVANCE: IVIG was effective in ameliorating allergic airway disease in our model. IVIG may be a promising adjunct therapy requiring further study for patients with severe asthma. CI - (c) 2011 Blackwell Publishing Ltd. FAU - Kaufman, G N AU - Kaufman GN AD - Meakins Christie Laboratories, Montreal, QC, Canada. FAU - Massoud, A H AU - Massoud AH FAU - Audusseau, S AU - Audusseau S FAU - Banville-Langelier, A-A AU - Banville-Langelier AA FAU - Wang, Y AU - Wang Y FAU - Guay, J AU - Guay J FAU - Garellek, J A AU - Garellek JA FAU - Mourad, W AU - Mourad W FAU - Piccirillo, C A AU - Piccirillo CA FAU - McCusker, C AU - McCusker C FAU - Mazer, B D AU - Mazer BD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110124 PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Serum Albumin) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Asthma/chemically induced/*immunology MH - Bronchial Hyperreactivity/immunology/*therapy MH - Disease Models, Animal MH - Humans MH - Immunoglobulins, Intravenous/immunology/*therapeutic use MH - Injections, Intraperitoneal MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - *Models, Immunological MH - Ovalbumin MH - Serum Albumin/administration & dosage/immunology MH - T-Lymphocytes, Regulatory/immunology EDAT- 2011/01/25 06:00 MHDA- 2012/06/30 06:00 CRDT- 2011/01/25 06:00 PHST- 2011/01/25 06:00 [entrez] PHST- 2011/01/25 06:00 [pubmed] PHST- 2012/06/30 06:00 [medline] AID - 10.1111/j.1365-2222.2010.03663.x [doi] PST - ppublish SO - Clin Exp Allergy. 2011 May;41(5):718-28. doi: 10.1111/j.1365-2222.2010.03663.x. Epub 2011 Jan 24.