The effects of central interleukin-1 signaling on peripheral immunomodulation.

摘要

Heroin administration suppresses the production of nitric oxide (NO), which is a molecule active in host defense against infection and disease. Previous research in our laboratory has demonstrated that the immunosuppressive effects of heroin can be conditioned by repeatedly pairing heroin administration with a unique environmental context. Re-exposure to the previously drug-paired context can illicit immunosuppressive effects similar to heroin administration alone. In addition, our laboratory has reported that the basolateral amygdala (BLA) and medial nucleus accumbens shell (mNAcS) are critical neural substrates that mediate this conditioned effect. The study presented in Chapter 2 revealed the presence of interleukin-1beta (IL-1beta) immunoreactivity in the BLA and mNAcS across various time points following re-exposure to a previously drug-paired environment; however, there were no differences in the level of IL-1beta expression. Chapter 3 demonstrated that blockade of IL-1 signaling in the BLA, but not CPu or mNAcS, attenuates heroin-conditioned immunosuppression of NO production and inducible nitric oxide synthase (iNOS) mRNA expression in spleen tissue. Chapter 4 found that intra-BLA administration of various doses of IL-1beta had no effect on NO production or iNOS mRNA expression following an immune challenge. Taken together, these findings suggest that IL-1 signaling in the BLA is necessary for the expression of heroin-conditioned immunosuppression of NO and iNOS mRNA. In addition, these findings indicate that exogenous IL-1beta administration into the BLA does not alter the peripheral induction of NO in blood plasma or iNOS mRNA expression in spleen tissue following an immune challenge.