Prenatal fluoxetine exposure affects cytokine and behavioral response to an immune challenge

• Effects of prenatal fluoxetine on the response to endotoxin were assessed in adult offspring mice.
• Prenatal fluoxetine reduced interleukin-6 and tumor necrosis factor-α response to endotoxin.
• Prenatal fluoxetine augmented interleukin-1β response to endotoxin.
• Prenatal fluoxetine diminished endotoxin-induced sickness behavior.
• The effects of prenatal fluoxetine were sex-dependent and age-specific.

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) is a commonly prescribed antidepressant drug in pregnant women. FLX readily crosses the placenta, consequently altering serotonergic neurotransmission in the fetus and causing physiological and behavioral disturbances in the newborn. Studies have shown that serotonin plays a role in modulating immune signaling. Thus, the goal of this study was to assess the effects of prenatal exposure to FLX on the response to an immune challenge in offspring mice. Male and female mice were prenatally exposed to FLX and later injected with lipopolysaccharide (LPS) at different stages of development. Results indicated that prenatal FLX modulated aspects of the response to the endotoxin challenge. Prenatal FLX diminished the secretion of interleukin (IL)-6 in adult male and female mice. Prenatal exposure to FLX further suppressed TNFα and augmented IL-1β secretion in adult males. Early effects of LPS (within 24 h of administration) on body weight and food consumption were diminished by prenatal exposure to FLX in adult mice. Delayed effects of LPS (within 60 h of administration) were modulated by prenatal FLX in young animals. These results provide an indication that prenatal modulations of the serotonergic system had lasting implications for host response to an immune challenge. These findings may contribute to the understanding of the effects of prenatal environment on the development of physiological systems that are important to coping with infectious challenges, and assist in understanding the limitations and precautions that should be taken in the use of SSRIs during pregnancy.