Long-lasting impact of early life immune stress on neuroimmune functions

Fever is one major cardinal sign of disease. It results from an intricate interplay between the immune system and the central nervous system. Bacterial or viral infections activate peripheral immune competent organs which send inflammatory signals to the brain and lead to an increase in body temperature. The increased body temperature creates a conducive environment to optimize the body's fight against the infection. A large body of experimental evidence suggests that early life bacterial or viral infections can lead to a long-lasting impact on this natural febrile response. The early life pathogenic encounter heightens the hypothalamic-pituitary-adrenal axis response, dampens the innate immune system, and consequently reduces the febrile response to a subsequent immune challenge during adulthood. This 'programming' effect operates only when such early life immune challenges occur during a critical window of either prenatal or postnatal development. In this review, the mechanisms underlying the long-lasting impact of perinatal immune challenge on adult fever are addressed.