Direct Influence of Mild Hypothermia on Cytokine Expression and Release in Cultures of Human Peripheral Blood Mononuclear Cells

Abstract

Hypothermia is associated with elevated frequency of infectious complications. Dysfunction of the immune response caused by hypothermia has been demonstrated in both clinical and animal studies, but it still remains unclear to what extent immunocompetent cells are directly influenced by hypothermia. To estimate the direct influence of mild hypothermia on cytokine expression and release by human peripheral blood mononuclear cells (PBMC), primary cultures of PBMC were incubated at 34 degrees C or 32 degrees C activated by lipopolysaccharide (LPS), phytohemagglutinin (PHA), or tumor necrosis factor-alpha (TNF-alpha). The cytokine gene expression was evaluated by RT-PCR. Release of interleukin-2 (IL-2), IL-6, IL-10, and TNF-alpha was measured by ELISA. Mild hyperthermia significantly impaired IL-2 gene expression in PHA-stimulated cultures of PBMC and decreased IL-2 release in all variants of cultures. Secretion of IL-6, IL-10, and TNF-alpha was decreased in hypothermic cultures of PBMC stimulated with the T lymphocyte activator PHA. Slight suppression of IL-10 secretion was observed also in TNF-alpha-stimulated hypothermic cultures of PBMC. TNF-alpha release increased slightly in mild hypothermia control cultures. Our data demonstrate that the direct influence of hypothermia on cytokine expression and release from PBMC is not uniform. Reduction of IL-2 production might play a crucial role in the impairment of immune response in hypothermia.

Pivotal role of Interleukin-10 on microRNA-155 expression in regulation of the monocyte response in hypothermia.

“…One of the most consistent results is the effect of hypothermia on cytokine expression in human monocytes or peripheral blood mononuclear cells (PBMCs) cultu res . Hypothermia reduces the initial secretion of early, pro-inflammatory cytokines compared to 3rC, but results in an increased and prolonged secretion of TNF-o, IL-1 ~ and IL-6 24h or longer after initial stimulation (18,20,23,62,(160)(161)(162)(163). In contrast to the pro-inflammatory cytokines, the expression of IL-10 was found to be reduced under hypothermic conditions in the same studies and some others (21,164).…”

“…Hypothermia has been shown to affect the secretion of cytokines (18,20,161). The available data of human cell cultures indicates that hypothermia diminishes the early response but results in a prolonged and increased production of pro-inflammatory cytokines.…”

“…There is an on-going debate, which part of the response is clinically more important. Depending on the focus of the authors, some reports underline the diminished pro-inflammatory response in the early phase (20,178). Others believe that the prolonged and sustained secretion of pro-inflammatory cytokines is more important and will have long lasting effect on the ability of the host to fight infections.…”

“…The available data in human in vitro cultures indicate that hypothermia results in a delayed, but increased and prolonged secretion of pro-inflammatory cytokines after LPS stimulation (18,20,161,163). In contrast, hypothermia decreases the production of antiinflammatory cytokines such as IL-10 (21,22,163).…”

“…Other investigators found impaired dendritic cell function in hypothermia, a cell with a pivotal role in the initiation of the immune response (17). Differences in pro-and anti-inflammatory cytokine 1 production between hypo-and normothermic conditions have been reported by several groups, although some of these results are contradictory (18)(19)(20)(21)(22).…”