Mild hypothermia inhibits IL-10 production in peripheral blood mononuclear cells.
BACKGROUND
Hypothermia is often associated with compromised host defenses and infections. Deterioration of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. Therefore, we determined whether mild hypothermia affects the production of several types of cytokines in peripheral blood mononuclear cells (PBMCs), and the balance between pro-inflammatory and anti-inflammatory states.


METHODS
PBMCs obtained from 12 healthy humans were cultured with phytohemagglutinin (PHA) in normothermic (37 degrees C: control) or hypothermic (33 degrees C) conditions for 24 h. The production levels of tumor necrosis factor (TNF)-alpha, the interleukins (ILs) IL-6, IL-8 and IL-10, and interferon (IFN)-gamma in the culture supernatants were measured by means of enzyme-linked immunosorbent assay (ELISA).


RESULTS
Under hypothermic conditions (33 degrees C), PHA-induced production of IL-10 and IFN-gamma in PBMCs was significantly lower, by 34% and 84%, respectively, when compared with controls, while production of TNF-alpha, IL-6 and IL-8 did not change. The magnitude of reduction of IL-10 in hypothermic conditions resulted in IL-10/pro-inflammatory cytokine ratios decreasing to approximately 30-45% of those of controls.


CONCLUSIONS
The present study clearly demonstrates that mild hypothermia (33 degrees C) inhibits IL-10 and IFN-gamma production in cultured PBMCs. The profound inhibition of IL-10 and the pro-inflammatory reaction-dominated state induced suggests that the host defense mechanism against secondary infection may be maintained rather than inhibited in hypothermia. Thus, the reduction of IL-10 could be an important characteristic of immune responses in mild hypothermia.
Matsui
T
T
Department of Laboratory Sciences, Yamaguchi University School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan. giants-ygc@umin.ac.jp
Ishikawa
T
T
Takeuchi
H
H
Tsukahara
M
M
Maekawa
T
T
D000328:Adult; D005260:Female; D006801:Humans; D007035:Hypothermia / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma