title: Methamphetamine administration targets multiple immune subsets and induces phenotypic alterations suggestive of immunosuppression.
abstract: Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells possessed a phenotype suggesting reduced responsiveness. Dendritic cells (DCs) and Gr-1(high) monocytes/macrophages were also decreased in abundance while Gr-1(low) monocytes/macrophages appear to show signs of perturbation. CD4 and CD8 T cell subsets were affected by methamphetamine, both showing a reduction in antigen-experienced subsets. CD4 T cells also exhibited signs of activation, with increased expression of CD150 on CD226-expressing cells and an expansion of KLRG1(+), FoxP3(-) cells. These results exhibit that meth has the ability to disrupt immune homeostasis and impact key subsets of leukocytes which may leave users more vulnerable to pathogens.
authors.affiliation: Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, Nebraska, United States of America. rharms@unmc.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Harms
authors.forename: Brenda
authors.initials: B
authors.lastname: Morsey
authors.forename: Craig W
authors.initials: CW
authors.lastname: Boyer
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
authors.forename: Nora
authors.initials: N
authors.lastname: Sarvetnick
mesh_terms: D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology*; D005434:Flow Cytometry; D016867:Immunocompromised Host; D016130:Immunophenotyping; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D008694:Methamphetamine