title: Early expression of cytokines in lymph nodes after treatment in vivo with Staphylococcus enterotoxin B.
abstract: Excessive cytokine expression induced by superantigen may be one aspect of the pathophysiology associated with Gram positive bacteremia. We have undertaken a study of the kinetics of cytokine production in lymph nodes obtained from in vivo Staphylococcus enterotoxin B (SEB) treated animals. This study was designed to evaluate the short term cytokine profile observed using immunohistochemistry (IHC) in BALB/c mice injected intraperitoneally (i.p.). The observed immunohistochemical kinetic profiles were corroborated using reverse transcription-polymerase chain reaction (RT-PCR) RNA analysis. We report here that TNF, IL-2, and IFN-gamma are the principal cytokines which were detected within hours of SEB administration, and that other cytokines such as IL-3, IL-4, IL-5, IL-6, IL-10, GM-CSF and M-CSF were undetectable. TNF and IL-2 appeared very early following SEB priming, and were observed by 1 h. IFN-gamma which appeared later (maximally at 14 h) was produced predominantly by CD8+ cells. In contrast, the TNF and IL-2 were produced primarily by CD4+ cells. Identical results were obtained by IHC and RT-PCR; the kinetics of mRNA expression slightly preceded the appearance of protein. The TNF and IFN-gamma staining patterns observed in lymph node sections were indicative of Golgi-localized cytokine. The IL-2 staining pattern observed in lymph node sections was distinctive, covering a significant local area of cells. This local regional concentration of IL-2, which may result from cytokine attached to extracellular binding components, may be an important aspect of the activation phase of a developing immune response. Rapid induction and excessive cytokine production elicited by superantigen in vivo, may ultimately help to explain the shock and death associated with SEB.
authors.affiliation: Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
authors.forename: M J
authors.initials: MJ
authors.lastname: Litton
authors.forename: B
authors.initials: B
authors.lastname: Sander
authors.forename: E
authors.initials: E
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: O'Garra
authors.forename: J S
authors.initials: JS
authors.lastname: Abrams
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005629:Frozen Sections; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal