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Interleukin (IL) 1beta, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: pathophysiological implications.

Abstract：

:The pathophysiology of systemic inflammation and sepsis involves peripheral organs, causing gastrointestinal, renal, and cardiovascular alterations, as well as the central nervous system (CNS), affecting sleep, temperature regulation, behavior, and neuroendocrine function. The molecular basis of the CNS effects of systemic inflammation are not fully elucidated. Here we show that the CNS responds to systemic inflammation with pronounced IL-1beta gene expression and limited IL-1 receptor antagonist (IL-1ra), IL-10, and IL-13 gene expression. This pattern occurs throughout the CNS, including areas such as the subfornical organ, pineal gland, neurohypophysis, and hypothalamus. In contrast, in the anterior pituitary, we found limited IL-1beta gene expression but marked induction of the mRNA encoding for the secreted isoform of IL-1ra, secreted IL-1ra. We conclude that the central manifestations of peripheral inflammation are mediated by endogenous brain IL-1beta synthesized during systemic inflammation in the context of limited central cytokine counter regulation of IL-1. As IL-1beta is a potent stimulus for inducible nitric oxide synthase expression and activity, these findings explain our previous observation that systemic inflammation promotes inducible nitric oxide synthase gene expression in the brain and the spillover of NO metabolites into cerebrospinal fluid. The CNS transcription of the HIV-1 replication factor IL-1beta in the context of limited transcription of the IL-1 replication inhibitors IL-1ra, IL-10, and IL-13 might help explain the negative impact of systemic inflammation on the clinical course of AIDS. In addition, we propose that IL-1ra may be secreted by the anterior pituitary as a systemic anti-inflammatory hormone that is released in response to IL-1beta originated from multiple sources.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Wong ML,Bongiorno PB,Rettori V,McCann SM,Licinio J

doi

10.1073/pnas.94.1.227

subject

Has Abstract

pub_date

1997-01-07 00:00:00

pages

227-32

issue

eissn

0027-8424

issn

1091-6490

journal_volume

pub_type

杂志文章

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Interleukin (IL) 1beta, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: pathophysiological implications.