Cell type-specific variations in the induction of hsp70 in human leukocytes by feverlike whole body hyperthermia

Fever has been associated with shortened duration and improved survival in infectious disease. The mechanism of this beneficial response is still poor ly understood. The heat-inducible 70-kDa heat shock protein (Hsp70) has bee n associated with protection of leukocytes against the cytotoxicity of infl ammatory mediators and with improved survival of severe infections. This st udy characterizes the induction of Hsp70 by feverlike temperatures in human leukocytes in vitro and in vivo. Using flow cytometry, Hsp70 expression wa s determined in whole blood samples. This approach eliminated cell isolatio n procedures that would greatly affect the results. Heat treatment of whole blood in vitro for 2 hours at different temperatures revealed that Hsp70 e xpression depends on temperature and cell type; up to 41 degreesC, Hsp70 in creased only slightly in lymphocytes and polymorphonuclear leukocytes. Howe ver, in monocytes a strong induction was already seen at 39 degreesC, and H sp70 levels at 41 degreesC were 10-fold higher than in the 37 degreesC cont rol. To be as close as possible to the physiological situation during fever , we immersed healthy volunteers in a hot water bath, inducing whole body h yperthermia (39 degreesC), and measured leukocyte Hsp70 expression. Hsp70 w as induced in all leukocytes with comparable but less pronounced cell type- specific variations as observed in vitro. Thus, a systemic increase of body temperature as triggered by fever stimulates Hsp70 expression in periphera l leukocytes, especially in monocytes. This fever-induced Hsp70 expression may protect monocytes when confronted with cytotoxic inflammatory mediators , thereby improving the course of the disease.