CYTOKINE PRODUCTION AFTER WHOLE-BODY AND LOCALIZED HYPERTHERMIA

The levels of TNF, IL-1 and IL-6 in circulating blood female WAG/Ry ra ts were assessed in relation to treatment with localized hyperthermia of the right hind leg or with whole-body hyperthermia (WBH). After a l ocalized treatment for 30 min at 43 or 44 degrees C no detectable incr ease in levels of IL-6 or TNF was obtained. Hyperthermia for 30 min at 45 degrees C led to an elevated level of IL-6 of 19.4 +/- 5.2 U/ml ab ove the control level 24 h after treatment. Levels of IL-I were never higher than those in control animals that received only anaesthesia. A naesthesia induced a peak level of approximately 131 U/ml IL-1 6 h aft er treatment. Serum levels of IL-1 and IL-6 are enhanced after WBH. IL -1 reaches a peak level already during WBH about 15 after reaching 41. 5 degrees C. IL-6 levels were not enhanced during WBH but 1 h after WB H a clear peak was observed. Anaesthesia with sham WBH did not lead to enhanced IL-6 levels but enhanced IL-I levels were clearly detected. We did not detect TNF in any sample after WBH. It is concluded from th e present results that IL-6 is not induced by a 'standard' treatment o f localized hyperthermia as used in oncotherapy (i.e. 60 min at 43 deg rees C) to such a high level locally that this is reflected in increas ed levels in circulating blood. WBH at clinically relevant temperature s leads to enhanced levels of IL-1 and IL-6. The difference in IL-6 re sponse after WBH or localized hyperthermia probably is related to the fact that in WBH also the bone marrow is treated. This may lead to sti mulation of this important stem cell compartment of the peripheral blo od. The sequence of appearance of IL-I and IL-6 after hyperthermia is akin to the sequence in an inflammatory response. However, the experim ents with sham treatment show that IL-I may appear in the circulating blood not followed by IL-6. These results indicate that enhanced IL-1 levels may reflect a stress reaction of the animal related to the (sha m) treatment. Enhanced levels of IL-1 after WBH correlate with enhance d levels of ACTH in the circulating blood.