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Immunomodulatory role of the corticotropin releasing factor

100%

Radulovic M., Spiess J.

Archivum Immunologiae et Therapiae Experimentalis

2001

vol. 49

issue 1

33-38

Corticotropin-releasing factor (CRF) was originally identified as a hypothalamic peptide which stimulates secretion of the hypophyseal adrenocorticotropic hormone. CRF exhibits its actions through G protein-dependent seven-membrane-domain receptors. Two subtypes of CRF receptors (CRFR1 and CRFR2) have been characterized thus far. CRF and its receptors were found in a number of brain regions, where they function by neuromodulation, and also in several peripheral organs. Besides CRF, another naturally occurring CRF-like peptide, urocortin, has been characterized. In the immune system, CRF and CRFR1 have so far been detected at both mRNA and protein lelvels in several lymphoid organs and at sites of inflammation. Locally injected CRF was shown to modulate the severity of inflammation. This effect was not only a result of hemodynamic changes known to be induced by CRF or by activation of the hypothalamo-pituitary adrenal axis, as CRF-binding sites were also found on immune cells. CRF was shown to directly modulate secretion of cytokines and neuropeptides, proliferation, chemotaxis and degranulation of purified macrophage and lymphocyte populations in vitro . The presence of functional CRFR was more recently demonstrated also on polymorphonuclear cells and significant amounts of CRF were shown to be produced in lymphoid organs, or delivered to lymphoid organs by peripheral nerves. Taken together, the experimental results obtained so far strongly point to the importance of CRF as a signaling molecule in lymphoid tissues and at the sites of inflammation.

Effects of infusion of corticotropin-releasing factor antagonist into the locus coeruleus on freezing behavior and brain catecholamines in rats

86%

Swiergiel A.

Acta Neurobiologiae Experimentalis

2003

vol. 63

issue 1

9-16

Administration of 0.2 mug of alpha-helical CRF9-41 (corticotropin-releasing factor receptor antagonist, ahCRF9-41) into the locus coeruleus (LC) region significantly reduced footshock-induced freezing behavior in adult male rats. Changes in the concentrations of noradrenaline (NA), dopamine and their catabolites in cortex, hippocampus and hypothalamus of footshocked rats were reminiscent of those observed in stressed animals. Rats injected with ahCRF prior to footshock displayed cerebral catecholamine responses that were not different from controls injected with vehicle. The results confirm earlier findings that CRF receptors at the LC region may mediate freezing and behavioral expression of fear. However, the results also suggest that though CRF receptors within the LC region mediate footshock-induced behavior, they are not necessarily involved in the short-term catecholamine response to footshock.

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1 Acta Neurobiologiae Experimentalis

1 Archivum Immunologiae et Therapiae Experimentalis

1 2003

1 2001

1 Radulovic M.

1 Spiess J.

1 Swiergiel A.

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Immunomodulatory role of the corticotropin releasing factor

Effects of infusion of corticotropin-releasing factor antagonist into the locus coeruleus on freezing behavior and brain catecholamines in rats