Tofacitinib treatment in primary herpes simplex encephalitis interferes with anti-viral response.

• Tofacitinib, a Janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis (RA). Herpes simplex virus type 1 (HSV-1) may cause encephalitis during primary infection or following reactivation from a latent state. Long-term tofacitinib treatment may increase the risk of this life-threatening condition. The aim of this study was to investigate the effect of tofacitinib on HSV-1 primary infection using a mouse model. Mice pre-treated with tofacitinib were intranasally infected with a clinical strain of HSV-1 and monitored for infection severity and anti-viral response. Tofacitinib treatment of HSV-1 primary infection resulted in increased viral loads and worsened clinical outcome. Furthermore, tofacitinib promoted M2 anti-inflammatory phenotype of microglia and infiltrating monocytes as well as inhibited production of inflammatory and antiviral cytokines by macrophages in vitro. Our findings show that treatment with tofacitinib increases severity of HSE in mice, by impairing anti-viral response induced by monocytes and microglia.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Nyckelord

herpes simplex virus

microglia; monocytes

tofacitinib

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)