Prior Viral Infection Increases Heat Stroke Severity in Mice

Anecdotal evidence suggests that prior viral or bacterial infection increases heat stroke (HS) severity. We hypothesized that (1) Poly I:C (PIC; 100 mg, IP) or lipopolysaccharide (LPS; 50 mg/kg, IP) injection 48h or 72h prior to heat exposure (HE) would exacerbate core temperature (T c ; radiotelemetry; ±0.1°C) responses and HS severity of male C57BL/6J mice, and (2) these responses would occur in the absence of overt PIC or LPS sickness behaviors. PIC and LPS induced 2.0°C and 1.1°C fevers, respectively, and decreased activity (ACT) compared to saline (SAL; equivalent volume). PIC caused greater body weight (BW), food intake (FI) and water intake (WI) loss than LPS. T c , ACT, BW, FI and WI of LPS mice were similar to SAL by 48h. FI and WI of PIC mice were similar to SAL by 72h; however, BW of PIC mice did not recover to pre‐injection levels by 72h. Heating time (190 min), thermal load (181°C·Min) and dehydration (9.6%) during HE were similar between PIC, LPS and SAL mice. PIC was associated with more severe HS recovery responses regardless of prior injection time. PIC injection 48h prior to HE decreased HS survival (60%) within ~4h of recovery and the PIC survivors showed a trend towards greater hypothermia depth (marker of HS severity; 30.4°C) compared to LPS (31.3°C) and SAL (31.5°C) mice. PIC injection 72h prior to HE had no effect on HS survival, but hypothermia depth was greater (29.2°C) compared to LPS (31.1°C) and SAL (31.2°C; ANOVA, P=0.022). Our data indicate that prior viral infection has no effect on T c responses during HE, but exacerbates HS severity during recovery even after sickness behaviors are no longer evident. Future studies will delineate the inflammatory pathways mediating decreased HS survival during the early stages of HS recovery. Author views not official US Army or DOD policy