title: Febrile temperatures attenuate IL-1 beta release by inhibiting proteolytic processing of the proform and influence Th1/Th2 balance by favoring Th2 cytokines.
abstract: 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-1beta release was inhibited at temperatures >38 degrees C, whereas intracellular proIL-1beta formation as well as the release of other cytokines except IL-18 were only attenuated above 42 degrees C, indicating that febrile temperatures impair the proteolytic processing of proIL-1beta. This attenuated processing is not due to either heat inactivation of caspase-1 or structural changes in proIL-1beta produced at higher temperatures. Instead, we propose that febrile conditions change cytosolic compartmentation or trafficking, so that synthesized proIL-1beta 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 degrees C compared with 37 degrees C. These results indicate that fever limits the production of the fever-inducing IL-1beta and also influences the adaptive immune response, favoring Th2 cytokine production.
authors.affiliation: Biochemical Pharmacology, University of Konstanz, Konstanz, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Boneberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
mesh_terms: D000942:Antigens, Bacterial / Q000494:pharmacology; D001831:Body Temperature; D020170:Caspase 1 / Q000378:metabolism / Q000502:physiology; D061945:Caspase Inhibitors; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation / Q000276:immunology*; D010450:Endopeptidases / Q000097:blood; D004768:Enterotoxins / Q000494:pharmacology; D005334:Fever / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000201:enzymology; D011498:Protein Precursors / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D061945:Caspase Inhibitors; D016207:Cytokines; D004768:Enterotoxins; D007375:Interleukin-1; D020382:Interleukin-18; D008070:Lipopolysaccharides; D011498:Protein Precursors; D011994:Recombinant Proteins; C031818:enterotoxin B, staphylococcal; D010450:Endopeptidases; D020170:Caspase 1