title: Diazepam leads to enhanced severity of orthopoxvirus infection and immune suppression.
abstract: Benzodiazepines are drugs widely used as tranquilizers and in various other indications. We treated Balb/c mice with diazepam and infected them with cowpox (CPXV) and vaccinia virus (VACV). Disease index, weight loss and the antibody response were determined. Additionally the influence of different benzodiazepines on the mitogen response of human peripheral blood lymphocytes and spleen cells was tested. Diazepam led to earlier disease onset, prolonged duration of symptoms, higher weight loss and overall disease index in VACV infected mice. CPXV infected mice developed poxviral skin lesions only after drug administration and a significant decrease in the specific antibody response was also observed. Diazepam and alprazolam also inhibited the proliferative response of human lymphocytes/spleen cells in vitro but did not show noteworthy apoptotic effects. It is surprising that even a single dose of diazepam has a profound influence on the immune system, sufficient to facilitate symptomatic infectious disease. These data provide first evidence that commonly used drugs like Valium may augment severity of rare poxvirus infections such as CPXV or monkeypox. As VACV is still used as life vaccine against smallpox there is also a risk of enhanced side effects or possible interference with the success of vaccination.
authors.affiliation: Department of Hygiene, Microbiology & Social Medicine, Innsbruck Medical University, Fritz-Pregl-Str. 3, R.301, A-6020 Innsbruck, Austria. hartwig.huemer@i-med.ac.at
authors.forename: Hartwig P
authors.initials: HP
authors.lastname: Huemer
authors.forename: Caroline
authors.initials: C
authors.lastname: Lassnig
authors.forename: Norbert
authors.initials: N
authors.lastname: Nowotny
authors.forename: Eveline U
authors.initials: EU
authors.lastname: Irschick
authors.forename: Maria
authors.initials: M
authors.lastname: Kitchen
authors.forename: Marion
authors.initials: M
authors.lastname: Pavlic
mesh_terms: D000525:Alprazolam / Q000009:adverse effects; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D017209:Apoptosis; D001835:Body Weight; D049109:Cell Proliferation; D002478:Cells, Cultured; D015608:Cowpox virus; D003975:Diazepam / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D011213:Poxviridae Infections / Q000473:pathology*; D013154:Spleen / Q000166:cytology; D014616:Vaccinia virus
chemical_list: D000914:Antibodies, Viral; D003975:Diazepam; D000525:Alprazolam