title: Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and Pentostam.
abstract: Successful treatment in allergic, autoimmune, and infectious diseases often requires altering the nature of a detrimental immune response mediated by a particular CD4+ T helper (Th) cell subset. While several factors contribute to the development of CD4+ Th1 and Th2 cells, the requirements for switching an established response are not understood. Here we use infection with Leishmania major as a model to investigate those requirements. We report that treatment with interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal drug Pentostam, induces healing in L. major-infected mice and that healing is associated with a switch from a Th2 to a Th1 response. The data suggest that decreasing antigen levels may be required for IL-12 to inhibit a Th2 response and enhance a Th1 response. These observations are important for treatment of nonhealing forms of human leishmaniasis and also demonstrate that in a chronic infectious disease an inappropriate Th2 response can be switched to an effective Th1 response.
authors.affiliation: Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Nabors
authors.forename: L C
authors.initials: LC
authors.lastname: Afonso
authors.forename: J P
authors.initials: JP
authors.lastname: Farrell
authors.forename: P
authors.initials: P
authors.lastname: Scott
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D018664:Interleukin-12 / Q000627:therapeutic use*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000628:therapy*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D018664:Interleukin-12; D000967:Antimony Sodium Gluconate