Tissue and circulating expression of IL-1 family members following heat stroke

Helwig BG, Leon LR. Tissue and circulating expression of IL-1 family members following heat stroke. Physiol Genomics 43: 1096-1104, 2011. First published August 9, 2011; doi: 10.1152/physiolgenomics.00076.2011.-Interleukin-1 (IL-1) is thought to have a significant role in the pathophysiology of heat stroke (HS), although little is known regarding the actions or expression patterns of the IL-1 family. This study tested the hypotheses that following HS IL-1 family gene expression is dynamic, while loss of IL-1 signaling enhances recovery. IL-1 family expression was determined in plasma, spleen, and liver from C57BL/6J mice (n = 24 control, n = 20 HS) at maximum core temperature (T-c,T-Max), hypothermia, and 24 h post-HS (24 h). Soluble IL-1 receptor subtype I (sIL-1RI) protein expression peaked at 24 h (14,659.01 +/- 2,016.28 pg/ml, P < 0.05), while sIL-1RII peaked at hypothermia (19,099.30 +/- 1,177.07 pg/ml). IL-1 alpha gene expression in the spleen (ninefold) and liver (fourfold) along with IL-1RI (threefold spleen and fivefold liver) were maximal at hypothermia. Spleen IL-1 beta gene expression peaked at T-c,T-Max (fourfold) but at hypothermia (fourfold) in liver. Gene expression of the IL-1 family member IL-18 peaked (2.5-fold) at T-c,T-Max but was similar at all other time points. Subsequent studies revealed that despite accruing a greater heating area (298 +/- 16 vs. 247 +/- 13 degrees C.min, P < 0.05), IL-1RI knockout (KO) mice (n = 14) showed an attenuated hypothermia depth (28.5 +/- 0.2 vs. 27.3 +/- 0.5 degrees C, P < 0.05) and duration (675 +/- 82 vs. 1,283 +/- 390 min, P < 0.05) with a higher 24 h T-c (36.9 vs. 34.1 degrees C, P < 0.05) compared with C57BL/6J mice (n = 8). The current results demonstrate that following HS IL-1 family gene expression is altered and IL-1RI KO mice display T-c responses consistent with a more rapid recovery.