Increased susceptibility of glutamine-depleted monocytes to fever-range hyperthermia: the role of 70-kDa heat shock protein.
OBJECTIVE
This study investigates the effect of fever-range hyperthermia on Gln-starving monocytes and the role of the 70-kDa heat shock protein Hsp70.


BACKGROUND
Fever is a protective acute-phase response to infection. However, in critically ill patients, the harmful effects of fever seem to be predominant. Critical illness is frequently associated with reduced plasma glutamine (Gln) levels, which contribute to the immune suppression in these patients due to impaired monocyte function.


METHODS
Isolated monocytes were suspended in Gln-depleted medium and exposed to 41 degrees C. Cell survival was determined by an MTT-based assay, and phagocytosis of Escherichia coli was measured by flow cytometry. Expression of Hsp70 was determined by Western blot.


RESULTS
Hyperthermia for 300 minutes strongly decreased the viability of Gln-depleted monocytes (85%), whereas it had only a moderate effect on Gln-supplied cells (45%, P < 0.05). Shorter treatments (45 minutes) of Gln-starving monocytes had almost no effects on viability but decreased the phagocytosis activity by 30.8%. In addition, the expression of Hsp70 was inhibited almost completely.


CONCLUSIONS
These data show that Gln-starving monocytes have a reduced thermoresistance. This suggests that elevated body temperature damages monocytes in critically ill patients with reduced plasma Gln-levels possibly via an inhibition of the cytoprotective protein Hsp70.
Pollheimer
Jürgen
J
Surgical Research Laboratories, Medical University of Vienna, Vienna, Austria.
Zellner
Maria
M
Eliasen
Maja Munk
MM
Roth
Erich
E
Oehler
Rudolf
R
D002470:Cell Survival / Q000502:physiology; D005334:Fever / Q000503:physiopathology*; D005434:Flow Cytometry; D005973:Glutamine / Q000097:blood*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology
D018840:HSP70 Heat-Shock Proteins; D005973:Glutamine