Heat stroke decreases cytokine and chemokine gene expression in the hypothalamus of rats (1104.15)

Abstract

We showed previously that rats display ~1°C core temperature (Tc) increase during ~4 days of heat stroke (HS) recovery; however, the mechanisms mediating this response remain unidentified. It was suggested that hypothalamic damage mediates this Tc response, but there is a lack of histological evidence in support of this. We hypothesized that local hypothalamic cytokines and/or chemokines, which are known regulators of Tc, may be mediating the elevation in Tc during HS recovery. The hypothalamus of Fischer 344 rats was examined for 83 cytokine/chemokine genes (real‐time PCR) at Tc,Max (41.8°C), 1, 3, and 10 days of HS recovery (3‐8 rats/group). IL‐1β was elevated ~14‐fold at Tc,Max and returned to baseline by 24 hours; IFNγ and IL‐10 were decreased ~3‐fold at 24 hours. All cytokines returned to baseline by 3 days. Most chemokines were downregulated ~2‐ to 4‐fold through 24 hours, but shifted towards increased expression by 3 days. Despite normal Tc at 10 days of recovery, some chemokine changes persisted. Contrary to our hypothesis, most cytokines/chemokines showed significant down regulation during HS recovery, which may indicate increased translation in our model. Importantly, resumption of normal Tc at 10 days with persistent alteration in the hypothalamic cytokine/chemokine profile may indicate greater susceptibility to a subsequent HS event. Author views not official US Army or DoD policy.