title: Beryllium, an adjuvant that promotes gamma interferon production.
abstract: Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.
authors.affiliation: Pulmonary, Allergy & Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.forename: O
authors.initials: O
authors.lastname: Atochina
authors.forename: B
authors.initials: B
authors.lastname: King
authors.forename: L
authors.initials: L
authors.lastname: Taylor
authors.forename: M
authors.initials: M
authors.lastname: Elloso
authors.forename: P
authors.initials: P
authors.lastname: Scott
authors.forename: M D
authors.initials: MD
authors.lastname: Rossman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage; D001608:Beryllium / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000008:administration & dosage; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D016207:Cytokines; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D001608:Beryllium