title: Rapamycin does not control hemophagocytic lymphohistiocytosis in LCMV-infected perforin-deficient mice.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is an immunodysregulatory disorder for which more effective treatments are needed. The macrolide rapamycin has immunosuppressive properties, making it an attractive candidate for controlling the aberrant T cell activation that occurs in HLH. To investigate its therapeutic potential, we used rapamycin to treat Lymphocytic Choriomeningitis Virus (LCMV)-infected perforin-deficient (Prf1(-/-)) mice according to a well-established model of HLH. At the regimens tested, rapamycin did not improve weight loss, splenomegaly, hemophagocytosis, cytopenias, or proinflammatory cytokine production in LCMV-infected Prf1(-/-) animals. Thus, single agent rapamycin appears ineffective in treating the clinical and laboratory manifestations of LCMV-induced HLH.
authors.affiliation: Division of Hematology/Oncology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Rothman
authors.forename: Rupali
authors.initials: R
authors.lastname: Das
authors.forename: David T
authors.initials: DT
authors.lastname: Teachey
authors.forename: Michele E
authors.initials: ME
authors.lastname: Paessler
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000188:drug therapy / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008217:Lymphocytic choriomeningitis virus; D051359:Lymphohistiocytosis, Hemophagocytic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin / Q000172:deficiency; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D054353:Perforin; D020123:Sirolimus