PMID- 16721274 OWN - NLM STAT- MEDLINE DCOM- 20060707 LR - 20071114 IS - 1073-2322 (Print) IS - 1073-2322 (Linking) VI - 25 IP - 6 DP - 2006 Jun TI - Intranasal exposure to staphylococcal enterotoxin B elicits an acute systemic inflammatory response. PG - 647-56 AB - Staphylococcus aureus produces a variety of superantigen exotoxins, including staphylococcal enterotoxin B (SEB). Little is known regarding the pathogenesis of SEB entering through the intranasal route. Intranasal exposure to SEB might occur because of nasal packing following surgical procedure, biologic warfare, or even S. aureus colonization. We evaluated the local and systemic effects of intranasally delivered SEB using a series of human leukocyte antigen (HLA) class II transgenic mice as conventional mice expressing endogenous class II molecules mount a poor immune response to SEB. Gene expression profiling using microarrays showed robust up-regulation of genes involved in several proinflammatory pathways as early as 3 h post-intranasal challenge with SEB in HLA class II transgenic mice. This was accompanied by a several hundred-fold increase in serum levels of pro-inflammatory cytokines such as IL-12, IL-6, TNF-alpha, IFN-gamma, as well as MCP-1 in HLA class II transgenic mice but not in C57BL/6 mice; CD4 or CD8 T-cells independently contributed to the systemic cytokine response. Defective IL-12 or IL-4 receptor signaling significantly decreased or increased serum IFN-gamma, respectively. Intranasal exposure to SEB resulted in neutrophil influx into bronchoalveolar lavage fluid and caused expansion of both CD4 and CD8 T-cells expressing TCR V beta 8 in the spleen. This was accompanied by mononuclear cell infiltration in the liver reminiscent of the systemic inflammatory response syndrome. Thus, we have shown, for the first time, that intranasal administration of SEB can cause systemic immune activation. FAU - Rajagopalan, Govindarajan AU - Rajagopalan G AD - Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. FAU - Sen, Moon M AU - Sen MM FAU - Singh, Manisha AU - Singh M FAU - Murali, Narayana S AU - Murali NS FAU - Nath, Karl A AU - Nath KA FAU - Iijima, Koji AU - Iijima K FAU - Kita, Hirohito AU - Kita H FAU - Leontovich, Alexey A AU - Leontovich AA FAU - Gopinathan, Unnikrishnan AU - Gopinathan U FAU - Patel, Robin AU - Patel R FAU - David, Chella S AU - David CS LA - eng GR - AI14764/AI/NIAID NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Shock JT - Shock (Augusta, Ga.) JID - 9421564 RN - 0 (Cytokines) RN - 0 (Enterotoxins) RN - 0 (HLA-DR3 Antigen) RN - 0 (Receptors, Interleukin-2) RN - 0 (Receptors, Interleukin-4) RN - 39424-53-8 (enterotoxin B, staphylococcal) SB - IM MH - Administration, Intranasal MH - Animals MH - CD4-Positive T-Lymphocytes MH - CD8-Positive T-Lymphocytes MH - Cytokines/immunology MH - Enterotoxins/administration & dosage/immunology/*toxicity MH - Gene Expression Regulation/drug effects/immunology MH - HLA-DR3 Antigen/genetics/*immunology MH - Humans MH - Inflammation/chemically induced/immunology/pathology MH - Lung/immunology/pathology MH - Mice MH - Mice, Knockout MH - Neutrophil Infiltration/drug effects/immunology MH - Receptors, Interleukin-2/deficiency/immunology MH - Receptors, Interleukin-4/deficiency/immunology MH - Signal Transduction/drug effects/immunology MH - Systemic Inflammatory Response Syndrome/chemically induced/*immunology/pathology EDAT- 2006/05/25 09:00 MHDA- 2006/07/11 09:00 CRDT- 2006/05/25 09:00 PHST- 2006/05/25 09:00 [pubmed] PHST- 2006/07/11 09:00 [medline] PHST- 2006/05/25 09:00 [entrez] AID - 00024382-200606000-00014 [pii] AID - 10.1097/01.shk.0000209565.92445.7d [doi] PST - ppublish SO - Shock. 2006 Jun;25(6):647-56. doi: 10.1097/01.shk.0000209565.92445.7d.