Prenatal opiate exposure attenuates LPS-induced fever in adult rats: role of interleukin-1beta.

Much is known about the immunomodulatory effects of opiate exposure and withdrawal in adult rats. However, little research has delved into understanding the immunological consequences of prenatal opiate exposure and postnatal withdrawal. The purpose of the current study was to measure changes in responding to immune stimulation in adult rats following prenatal opiate exposure. Further, we sought to characterize the role of interleukin (IL)-1beta in these changes. Following prenatal exposure to the long-acting opiate l-alpha-acetylmethadol (LAAM), adult male and female rats were assessed for their fever response to lipopolysaccharide (LPS). Blood and tissue samples were collected to measure circulating IL-1beta and IL-1beta protein in the hypothalamus and spleen. Prenatal LAAM exposure resulted in a blunted fever response to LPS injection without any changes in basal body temperature or in response to saline injection. Circulating IL-1beta was not affected by prenatal LAAM exposure, nor was IL-1beta protein in the spleen. Interestingly, mature IL-1beta protein was elevated in the hypothalamus of prenatally LAAM-treated rats. These results indicate that prenatal opiate exposure blunts the fever response of adult offspring. Direct action of IL-1beta is likely not the cause of the dysfunction reported here. However, alterations in signaling mechanisms downstream from IL-1beta may play a role in the altered fever response in adult rats treated prenatally with opiates.