Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury

Abstract

BackgroundAcute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion.MethodsTo address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to a closed head mild TBI (mTBI) by a standard controlled cortical impact, along with or without treatment of sphingosine 1-phosphate (S1P) or rolipram, after which the brain tissue of the impact site was evaluated for cell morphology via histology, inflammation by qRT-PCR and T cell staining, and cell death with Caspase-3 and TUNEL staining. Circulating lymphocytes were quantified by flow cytometry, and plasma hydrocortisone was analyzed by LC-MS/MS. To investigate the mechanism whereby cortisol lowered the number of peripheral T cells, T cell egress was tracked in lymph nodes by intravital confocal microscopy after hydrocortisone administration.ResultsWe detected a decreased number of circulating lymphocytes, in particular, T cells soon after mTBI, which was inversely correlated with a transient and robust increase of plasma cortisol. The transient lymphocytopenia might be caused by cortisol in part via a blockade of lymphocyte egress as demonstrated by the ability of cortisol to inhibit T cell egress from the secondary lymphoid tissues. Moreover, exogenous hydrocortisone severely suppressed periphery lymphocytes in uninjured mice, whereas administering an egress-promoting agent S1P normalized circulating T cells in mTBI mice and increased T cells in the injured brain. Likewise, rolipram, a cAMP phosphodiesterase inhibitor, was also able to elevate cAMP levels in T cells in the presence of hydrocortisone in vitro and abrogate the action of cortisol in mTBI mice. The investigation demonstrated that the number of circulating T cells in the early phase of TBI was positively correlated with T cell infiltration and inflammatory responses as well as cell death at the cerebral cortex and hippocampus beneath the impact site.ConclusionsDecreases in intracellular cAMP might be part of the mechanism behind cortisol-mediated blockade of T cell egress. The study argues strongly for a protective role of cortisol-induced immune suppression in the early stage of TBI.

Depletion of regulatory T cells increases T cell brain infiltration, reactive astrogliosis, and interferon-γ gene expression in acute experimental traumatic brain injury

“…Accordingly, effector CD4+ T cells adoptively transferred into T celland B cell-deficient recombination-activating gene 1 (RAG1) knockout mice exacerbated lesion size and apoptosis after brain injury [28]. Experimental studies in the early phase of TBI further indicated that the number of circulating T cells correlated with T cell infiltration and inflammatory responses as well as cell death beneath the impact site [29].…”

A pilot study of hyperoxemia on neurological injury, inflammation and oxidative stress

“…It promotes the reparation and regeneration processes of the primary injury; on the other hand, it may worsen secondary brain injury. 36 In our pilot study, even NSE concentrations were equal in both study groups, suggesting that hyperoxia in this complex setting does not negatively affect brain tissue.…”

Response to Lim et al regarding “In-flight transmission of measles: Time to update the guidelines?”

“…8 In addition, melatonin and cortisol play important roles in controlling responses to pathogens. 9,10 Craniofacial characteristics of the Asian population in the sample studied by the authors (Chinese subjects), may trigger sleep disorders. 11 All these factors affect immune health, wellbeing, and quality of life.…”