Suppression of the febrile response in late gestation: evidence, mechanisms and outcomes

Fever is a beneficial host defence response. However, fever caused by the immune stimulant, lipopolysaccharide (LPS), are attenuated in many species during pregnancy, particularly near term. A number of parallel mechanisms may be responsible, and these vary in magnitude according to the time of gestation, type of inflammatory stimulus and species of animal. Some studies report a reduction in the plasma levels of circulating pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-1beta and interleukin-6 along with increased levels of anti-inflammatory cytokines such as interleukin-1 receptor antagonist. Associated with the attenuated febrile response to LPS is a reduction in the activation of the prostaglandin synthesising enzyme, cyclo-oxygenase 2, resulting in reduced levels of the obligatory prostaglandin mediators of the febrile response in the brain. There is also a reduction in the sensitivity of the brain to the pyrogenic action of prostaglandins, which does not appear to be due to a change in the levels of hypothalamic EP3 prostaglandin receptors. The suppression of fever at term may be important for the health of the neonate because fever in pregnant mothers may be harmful to the late-term foetus and neonate.