Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation

Abstract

The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin‐releasing hormone (CRH) is a neuropeptide released from the hypothalamic–pituitary–adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates immune suppression, CRH has also been found to mediate inflammatory responses in peripheral tissues. Streptococcus pneumoniae is a microorganism commonly present among the commensal microflora along the upper respiratory tract. Transmission of disease stems from the resident asymptomatic pneumococcus along the nasal passages. Glucocorticoids are central mediators of immune suppression and are the primary adjuvant pharmacological treatment used to reduce inflammatory responses in patients with severe bacterial pneumonia. However, controversy exists in the effectiveness of glucocorticoid treatment in reducing mortality rates during S. pneumoniae infection. In this study, we compared the effect of the currently utilized pharmacologic glucocorticoid dexamethasone with CRH. Our results demonstrated that intranasal administration of CRH increases survival associated with a decrease in inflammatory cellular immune responses compared to dexamethasone independent of neutrophils. Thus, providing evidence of its use in the management of immune and inflammatory responses brought on by severe pneumococcal infection that could reduce mortality risks.

Interplay Between the Immune and Endocrine Systems in the Lung: Implications for TB Susceptibility

“…Limited information is available on how targeting CRH and CRHR activity in the respiratory tract impacts bacterial disease outcome. In a murine respiratory Streptococcus pneumoniae infection model, Burnley and Jones (2017) demonstrated that intranasal CRH administration reduces the pulmonary inflammatory response, and the subsequent recruitment of neutrophils and monocytes to the lung, improving survival in these animals ( 43 ). Moffat et al (2006) demonstrated that, urocortin, a structurally related peptide to CRH, causes bronchorelaxation and limits lipopolysaccharide (LPS)-induced pulmonary inflammation (specifically neutrophil recruitment) to a greater extent than CRH ( 44 ).…”