Corticotropin-Releasing Hormone Contributes to the Peripheral Inflammatory Response in Experimental Autoimmune Encephalomyelitis

• Published in: The Journal of immunology (1950) 2005-05, Vol.174 (9), p.5407-5413
• Main Authors: Benou, Christina, Wang, Yue, Imitola, Jaime, VanVlerken, Lilian, Chandras, Christina, Karalis, Katia P, Khoury, Samia J
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - genetics; Antigen Presentation - immunology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - pathology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cells, Cultured; Corticotropin-Releasing Hormone - antagonists & inhibitors; Corticotropin-Releasing Hormone - deficiency; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - physiology; Cytokines - biosynthesis; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Glucocorticoids - biosynthesis; I-kappa B Proteins - metabolism; Immunity, Innate - genetics; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - physiology; Lymphocyte Count; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-KappaB Inhibitor alpha; Phosphorylation; Receptors, Antigen, T-Cell - physiology; Severity of Illness Index; Spleen - immunology; Spleen - metabolism; Spleen - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; Th1 Cells - cytology; Th1 Cells - immunology; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.9.5407

Peripheral corticotropin-releasing hormone (CRH) is thought to have proinflammatory effects. We used the model of experimental autoimmune encephalomyelitis (EAE) to study the role of CRH in an immune-mediated disease. We showed that CRH-deficient mice are resistant to EAE, with a decrease in clinical score as well as decreased cellular infiltration in the CNS. Furthermore, Ag-specific responses of primed T cells as well as anti-CD3/anti-CD28 TCR costimulation were decreased in crh(-/-) mice with decreased production of Th1 cytokines and increased production of Th2 cytokines. Wild-type mice treated in vivo with a CRH antagonist showed a decrease in IFN-gamma production by primed T cells in vitro. This effect of CRH is independent of its ability to increase corticosterone production, because adrenalectomized wild-type mice had similar disease course and severity as control mice. We found that IkappaBalpha phosphorylation induced by TCR cross-linking was decreased in crh(-/-) T cells. We conclude that peripheral CRH exerts a proinflammatory effect in EAE with a selective increase in Th1-type responses. These findings have implications for the treatment of Th1-mediated diseases such as multiple sclerosis.