Low T3 Syndrome in Head-Injured Patients is Associated with Prolonged Suppression of Markers of Cell-Mediated Immune Response

Abstract

European Journal of Trauma Ab stractPurpose: To clarify the association between disturbed thyroid hormone metabolism (low T 3 syndrome) and release of cytokines and markers of cell-mediated immune response. Material and Methods: Concentrations of cytokines as well as of thyroid hormones were determined in 32 patients suffering from severe traumatic brain injury: interleukin-(IL-)1, IL-6, IL-10, tumor necrosis factor, transforming growth factor-(TGF-)β, soluble interleukin-2 receptor (sIL-2R), neopterin, and β 2 -microglobulin (β2m) in serum and cerebrospinal fluid; triiodothyronine (T 3 ), free T 3 , thyroxine (T 4 ), free T 4 , thyrotropin, thyroxine-binding globulin, and albumin in serum. Additionally, clinical parameters were assessed: Glasgow Coma Score, CT scan, intracranial pressure, Glasgow Outcome Score, and occurrence of pneumonia. Results: Among 31 patients with a low T 3 syndrome, those with additional low serum T 4 levels (n = 13) showed a prolonged suppression of serum β2m, neopterin, and sIL-2R, and a higher secondary increase of serum β2m, neopterin, and TGF-β, as well as lower T 3 levels (all p < 0.05). These patients also had a longer stay in the intensive care unit (34 ± 6 days vs. 22 ± 12 days; p = 0.008). Increased levels of β2m correlated with a preceding decrease of thyrotropin (cerebrospinal fluid: r = -0.53; p = 0.004; serum: r = -0.41; p = 0.029). Associations of thyroid hormone metabolism with either other cytokines or with clinical parameters were not detected. Conclusion:These results show that low T3 syndrome is a very common pathophysiological feature after severe traumatic brain injury. The association of a low T 3 syndrome in combination with low serum T 4 levels, with an altered time course of markers of cell-mediated immunity led the authors to hypothesize that a disturbed thyroid hormone metabolism may be interrelated with a prolonged cellular immune dysfunction after traumatic brain injury.

Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…While NTIS may be beneficial in the acute phase of critical illness, it is increasingly seen as maladaptive and hampering the recovery of patients in the case of prolonged critical illness (96,101,152,169,(171)(172)(173). Low thyroid hormone function may hamper the function of organs (170) and the activity of immune cells, including natural killer cells (174)(175)(176)(177)(178)(179)(180)(181)(182)(183)(184)(185). Immune dysfunctions might in turn explain other pathologies, such as viral reactivation observed in ICU patients (186)(187)(188).…”

Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…Reduced thyroid hormone function: The prolonged downregulation of thyroid hormone activity certainly has implications for the immune system. Authors describe the profound effects of circulating thyroid hormone levels on the activity of monocytes, lymphocytes macrophages, neutrophils, dendritic cells and natural killer cells; as well as cytokines (161)(162)(163)(164)(165)(166)(167)(168)(169)(170). Notably, depressed thyroid levels appear to depress the activity of natural killer cells (171)-a signature finding in ME/CFS (172).…”