Tumor necrosis factor and interleukin-6 in critical illness polyneuromyopathy

Critical illness myopathy serum fractions affect membrane excitability and intracellular calcium release in mammalian skeletal muscle

“…Also, a low molecular endogenous protein acting as a sodium channel blocker, ultimately turning out to be a pentapeptide, has been identified in the cerebrospinal fluid of patients with inflammatory autoimmune disorders of the nervous system [55]. Other authors have also postulated a factor inducing myopathy in the serum of patients suffering from CIM [31]. The factor causing the effects observed in our experiments might be a small polypeptide or a lipophilic substance, e. g. a fatty acid, as protein SDS pages did not show differences between CIM and control serum.…”

“…So far, studies done in patients with CIM can indicate a more puzzling situation as administration of glucocorticoids and neuromuscular blocking agents has been found not always to result in the development of CIM [26] although these drugs are widely accepted as trigger agents which have been tested on established animal models [27][28][29][30]. Moreover, patients given steroids may recover from CIM even when steroids were not discontinued [26].Also, cytokines (tumour necrosis factor-α and interleukin-6) which it has been suggested are involved in the pathogenesis of CIM [3] were not convincingly increased in the sera of affected patients [31].Direct electrical stimulation revealed reduced muscular excitability in clinical patients [27]. In an animal model, abnormalities of sodium channel inactivation have been found [28] whereas in animals having undergone high-dose corticosteroid treatment the membrane effects seemed to be more complex [29].Very recently,inactivation of sodium channels has been correlated with depolarised resting potentials and to be crucially responsible for reduced membrane excitability in the rat animal model of critical illness myopathy for steroid denervated muscle fibres [30].…”

The Role of Local and Systemic Inflammation in the Pathogenesis of Intensive Care Unit-acquired Weakness

“…Plasma IL-10, insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein-1 (IGFBP)-I and IGFBP-III levels were not independently associated with ICU-acquired weakness. In an earlier study, plasma IL-6 and TNFlevels measured in ICU patients after a diagnosis of ICU-acquired weakness were not different from control ICU patients (in whom plasma was measured during the first or second week of ICU-admission) [20]. A correlation between plasma IL-2 receptors and reduction in the amplitude of the compound motor action potential (CMAP) in the median and tibial nerves was found in another study [11].…”

Neurological Sequelae of Sepsis: II) Neuromuscular Weakness

“…A significant correlation between serum concentration of endotoxin and interleukin-2-receptors (IL2-R) and the reduction of compound motor action potentials in electroneurography has been found recently [38]. Significantly elevated levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were found in patients with CIP compared to controls [39]. Druschky et al found neurotoxicity in 12 of 16 CIP patients in an in-vitro serum toxicity assay on cultured rat motoneurons [40].…”