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      Regulation of the Hypothalamic-Pituitary-Adrenal Axis by Cytokines: Actions and Mechanisms of Action

      1 , 1

      Physiological Reviews

      American Physiological Society

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          Most cited references 743

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          Subregion- and cell type-restricted gene knockout in mouse brain.

          Using the phage P1-derived Cre/loxP recombination system, we have developed a method to create mice in which the deletion (knockout) of virtually any gene of interest is restricted to a subregion or a specific cell type in the brain such as the pyramidal cells of the hippocampal CA1 region. The Cre/loxP recombination-based gene deletion appears to require a certain level of Cre protein expression. The brain subregional restricted gene knockout should allow a more precise analysis of the impact of a gene mutation on animal behaviors.
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            Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin

             C Rivier,  J Rivier,  J Spiess (1981)
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              MIF as a glucocorticoid-induced modulator of cytokine production.

              Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. Yet, in contrast to other hormonal systems, no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Recent investigations of the protein macrophage migration inhibitory factor (MIF), which was discovered originally to be a T-lymphocyte-derived factor, have established it to be a pro-inflammatory pituitary and macrophage cytokine and a critical mediator of septic shock. Here we report the unexpected finding that low concentrations of glucocorticoids induce rather than inhibit MIF production from macrophages. MIF then acts to override glucocorticoid-mediated inhibition of cytokine secretion by lipopolysaccharide (LPS)-stimulated monocytes and to overcome glucocorticoid protection against lethal endotoxaemia. These observations identify a unique counter-regulatory system that functions to control inflammatory and immune responses.
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                Author and article information

                Journal
                Physiological Reviews
                Physiological Reviews
                American Physiological Society
                0031-9333
                1522-1210
                January 1999
                January 1999
                : 79
                : 1
                : 1-71
                Affiliations
                [1 ]The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California; and North Western Injury Research Centre, University of Manchester, Manchester, United Kingdom
                Article
                10.1152/physrev.1999.79.1.1
                © 1999

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