Febrile Temperatures Attenuate IL-1{beta} Release by Inhibiting Proteolytic Processing of the Proform and Influence Th1/Th2 Balance by Favoring Th2 Cytokines

We investigated possible feedback mechanisms of febrile temperatures on LPS- and staphylococcal enterotoxin B (SEB)-induced cytokine release in human whole blood. LPS-induced IL-1[beta] release was inhibited at temperatures >38 degree C, whereas intracellular proIL-1[beta] formation as well as th...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2003-07, Vol.171 (2), p.664-668
Main Authors: Boneberg, Eva-Maria, Hartung, Thomas
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We investigated possible feedback mechanisms of febrile temperatures on LPS- and staphylococcal enterotoxin B (SEB)-induced cytokine release in human whole blood. LPS-induced IL-1[beta] release was inhibited at temperatures >38 degree C, whereas intracellular proIL-1[beta] formation as well as the release of other cytokines except IL-18 were only attenuated above 42 degree C, indicating that febrile temperatures impair the proteolytic processing of proIL-1[beta]. This attenuated processing is not due to either heat inactivation of caspase-1 or structural changes in proIL-1[beta] produced at higher temperatures. Instead, we propose that febrile conditions change cytosolic compartmentation or trafficking, so that synthesized proIL-1[beta] cannot encounter caspase-1. Febrile temperatures also influenced Th1/Th2 cytokine balance. We observed a 3-fold increase in the Th2-cytokines IL-5 and IL-13 and a reduction to 15% of the Th1-cytokine IL-2 when SEB-stimulated whole blood was incubated at 40 degree C compared with 37 degree C. These results indicate that fever limits the production of the fever-inducing IL-1[beta] and also influences the adaptive immune response, favoring Th2 cytokine production.
ISSN:0022-1767
1550-6606