title: Acute morphine administration reduces white blood cells' capability to induce innate resistance against HSV-1 infection in BALB/c mice.
abstract: OBJECTIVE
  It has been reported that acute morphine administration modulates innate immune response to herpes simplex virus 1 (HSV-1) infection. In this study, the effect of acute morphine on innate resistance and its probable mechanisms in increasing the mortality rate during HSV-1 infection were investigated.
  
  
  METHODS
  Mice were infected with HSV-1 24 h prior to different doses of morphine or saline administration and the mortality rate was recorded. Spleen cells were obtained from morphine- or saline-treated mice, then natural killer (NK) cell activity and interferon-gamma (IFN-gamma) production were evaluated. The effect of morphine on white blood cells' capacity to induce protection against HSV-1 infection was evaluated by adoptive transfer of spleen cells to cyclophosphamide-treated mice that were previously infected with HSV-1. Furthermore, in a separate experiment, a different group of mice received corticosterone 24 h after HSV-1 infection.
  
  
  RESULTS
  Mortality rate in high-dose acute morphine-treated mice increased significantly compared to saline-treated mice (p = 0.035). NK cell cytotoxicity and IFN-gamma mRNA levels also showed a significant reduction compared to those of control groups (p < 0.001 and p = 0.014, respectively). Corticosterone administration reduces innate resistance against HSV-1 infection compared to saline-treated mice (p = 0.044). Furthermore, adoptive transfer of normal but not morphine-treated spleen cells induces resistance against HSV infection in cyclophosphamide-injected mice (p = 0.009).
  
  
  CONCLUSIONS
  The current study shows that acute morphine administration reduces white blood cells' capability to induce protection against HSV-1 infection via suppression of IFN-gamma production and NK cells activity. This may be due to the increase in corticosteroids. Further studies are needed to test the effect of acute morphine on other immune cells.
authors: Department of Virology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. jamali@modares.ac.ir
authors: Abbas
authors: A
authors: Jamali
authors: Taravat
authors: T
authors: Bamdad
authors: Hoorieh
authors: H
authors: Soleimanjahi
authors: Firouz Ghaderi
authors: FG
authors: Pakdel
authors: Ehsan
authors: E
authors: Arefian
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects*; D007371:Interferon-gamma / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000009:adverse effects*; D009294:Narcotics / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D009294:Narcotics; D012333:RNA, Messenger; D009020:Morphine; D007371:Interferon-gamma; D003345:Corticosterone