Medical Microbiology and Immunology

, Volume 207, Issue 2, pp 105–115 | Cite as

Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts

  • Vahid Salimi
  • Habib Mirzaei
  • Ali Ramezani
  • Alireza Tahamtan
  • Abbas Jamali
  • Shahram Shahabi
  • Maryam Golaram
  • Bagher Minaei
  • Mohammad Javad Gharagozlou
  • Mahmood Mahmoodi
  • Louis Bont
  • Fazel Shokri
  • Talat Mokhtari-Azad
Original Investigation


Opioid system plays a significant role in pathophysiological processes, such as immune response and impacts on disease severity. Here, we investigated the effect of opioid system on the immunopathogenesis of respiratory syncytial virus (RSV) vaccine (FI-RSV)-mediated illness in a widely used mouse model. Female Balb/c mice were immunized at days 0 and 21 with FI-RSV (2 × 106 pfu, i.m.) and challenged with RSV-A2 (3 × 106 pfu, i.n.) at day 42. Nalmefene as a universal opioid receptors blocker administered at a dose of 1 mg/kg in combination with FI-RSV (FI-RSV + NL), and daily after live virus challenge (RSV + NL). Mice were sacrificed at day 5 after challenge and bronchoalveolar lavage (BAL) fluid and lungs were harvested to measure airway immune cells influx, T lymphocyte subtypes, cytokines/chemokines secretion, lung histopathology, and viral load. Administration of nalmefene in combination with FI-RSV (FI-RSV + NL-RSV) resulted in the reduction of the immune cells infiltration to the BAL fluid, the ratio of CD4/CD8 T lymphocyte, the level of IL-5, IL-10, MIP-1α, lung pathology, and restored weight loss after RSV infection. Blocking of opioid receptors during RSV infection in vaccinated mice (FI-RSV-RSV + NL) had no significant effects on RSV immunopathogenesis. Moreover, administration of nalmefene in combination with FI-RSV and blocking opioid receptors during RSV infection (FI-RSV + NL-RSV + NL) resulted in an increased influx of the immune cells to the BAL fluid, increases the level of IFN-γ, lung pathology, and weight loss in compared to control condition. Although nalmefene administration within FI-RSV vaccine decreases vaccine-enhanced infection during subsequent exposure to the virus, opioid receptor blocking during RSV infection aggravates the host inflammatory response to RSV infection. Thus, caution is required due to beneficial/harmful functions of opioid systems while targeting as potentially therapies.


Respiratory syncytial virus Formalin-inactivated RSV Immunopathogenesis Opioids Nalmefene 



Respiratory syncytial virus


Formalin-inactivated RSV




µ-Opioid receptors


δ-Opioid receptors


κ-Opioid receptors


Phosphate buffer saline




Bronchoalveolar lavage


BAL fluid




Substance P



This work was supported by Iran National Science Foundation (No.88000497).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Vahid Salimi
    • 1
  • Habib Mirzaei
    • 1
  • Ali Ramezani
    • 1
  • Alireza Tahamtan
    • 1
    • 2
  • Abbas Jamali
    • 3
  • Shahram Shahabi
    • 4
  • Maryam Golaram
    • 5
  • Bagher Minaei
    • 6
  • Mohammad Javad Gharagozlou
    • 7
  • Mahmood Mahmoodi
    • 8
  • Louis Bont
    • 9
  • Fazel Shokri
    • 5
  • Talat Mokhtari-Azad
    • 1
  1. 1.Department of Virology, School of Public HealthTehran University of Medical SciencesTehranIran
  2. 2.Department of Microbiology, School of MedicineGolestan University of Medical SciencesGorganIran
  3. 3.Influenza and Other Respiratory Viruses DepartmentPasteur Institute of IranTehranIran
  4. 4.Cellular and Molecular Research CenterUrmia University of Medical SciencesUrmiaIran
  5. 5.Department of Immunology, School of Public HealthTehran University of Medical SciencesTehranIran
  6. 6.Department of Anatomy, Faculty of MedicineTehran University of Medical SciencesTehranIran
  7. 7.Department of Pathology, Faculty of Veterinary MedicineUniversity of TehranTehranIran
  8. 8.Epidemiology and Biostatistics Department, School of Public HealthTehran University of Medical SciencesTehranIran
  9. 9.Department of Paediatrics, Wilhelmina Children’s HospitalUniversity Medical Centre UtrechtUtrechtThe Netherlands

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