title: Glucocorticoids enhance interleukin-4 production to neo-antigen (hyaluronidase) in children immunocompromised with cytostatic drugs.
abstract: Immunoglobulin E (IgE)-mediated immediate-type allergic reactions to hyaluronidase have been observed in children with central nervous system (CNS) tumors. Glucocorticoids, used as therapy for brain edema, are discussed controversially as T helper 2 (Th2) stimulatory factors. In this study we investigated the role of glucocorticoids on a Th2 cytokine-promoting effect in children with CNS tumors. Peripheral blood mononuclear cells (PBMCs) from: 29 children suffering from malignant brain tumors, of whom 23 received short-term glucocorticoid treatment (for 3-4 days) during the course of chemotherapy; 18 children with nephrotic syndrome or renal transplantation receiving long-term glucocorticoid treatment; and 13 healthy children, were incubated with phytohemagglutinin (PHA) and/or anti-CD28 monoclonal antibody (mAb) and, in a second approach, with hyaluronidase. The concentrations of Th cell-mediated cytokines - interleukin (IL)-4, IL-10, and interferon-gamma (IFN-gamma) - were measured in supernatants. The IL-4 production of PBMCs incubated with PHA/anti-CD28 mAb from children with repeated co-administration of glucocorticoids, hyaluronidase, and cytostatic drugs (median: 249.9 pg/ml; range: 234.4-261.7) was significantly higher (p < 0.0001) than IL-4 production of PBMC from children of all the other groups (median: 86.18; range: 16.0-212.5). There was no significant difference in the levels of IL-10 and IFN-gamma within the groups. PBMCs stimulated only with hyaluronidase failed to produce detectable levels of cytokines. The results of this study indicate that repeated co-administration of glucocorticoids and hyaluronidase (a neo-antigen) enhance IL-4 production in vitro and thus may induce the production of specific IgE antibodies in children immunocompromised with cytostatic drugs. Hyaluronidase itself does not stimulate in vitro IL-4 synthesis in PBMCs of children receiving cytostatic drugs.
authors.affiliation: Department of Paediatrics, University of Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Edelbauer
authors.forename: Marianne
authors.initials: M
authors.lastname: Gerstmayr
authors.forename: Christine
authors.initials: C
authors.lastname: Loibichler
authors.forename: Eva
authors.initials: E
authors.lastname: Jost
authors.forename: Martina
authors.initials: M
authors.lastname: Huemer
authors.forename: Radvan
authors.initials: R
authors.lastname: Urbanek
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szépfalusi
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000276:immunology / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000276:immunology; D002648:Child; D002669:Child Welfare; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects* / Q000276:immunology; D003907:Dexamethasone / Q000276:immunology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000276:immunology / Q000627:therapeutic use*; D006681:HLA-D Antigens / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000276:immunology / Q000627:therapeutic use*; D016867:Immunocompromised Host / Q000187:drug effects* / Q000276:immunology; D007223:Infant; D007229:Infant Welfare; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D005938:Glucocorticoids; D006681:HLA-D Antigens; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma; D006821:Hyaluronoglucosaminidase