Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory

Figures & data

Figure 1 Systemic pretreatment with AMG517 (dose indicated) decreases survival of young mice in LPS-induced SIRS (A). Confirming an effective blockade of TRPV1 channels, the AMG517 pretreatment increases deep T_b in young mice (B).

Figure 2 Systemic pretreatment with AMG517 (dose indicated) increases survival of aged mice in LPS-induced SIRS (A). Confirming an effective blockade of TRPV1 channels, the AMG517 pretreatment increases deep T_b in aged mice (B).

Figure 3 Compared with their age-matched wild-type littermates, middle-aged Trpv1^−/− mice have a higher survival rate (A) and a lower serum TNFα concentration (B) during LPS-induced SIRS.

Figure 4 Compared with their age-matched wild-type littermates, middle-aged Trpv1^−/− mice have a shorter survival time (A) and a slower T_b recovery (B) during CLP-induced sepsis.

Table 1 Effects of age and TRPV1 antagonism on mortality in LPS-induced SIRS and CLP-induced sepsis

Model	Variable	Cox survival regression analysis			Logrank test		Time to death
		Hazard ratio of death	95% confidence interval	p	Score	p	Mean ± SE (h)	p
LPS	Aged vs. young	2.2	1.3 ÷ 3.1	<0.001	20.5	<0.001	16 ± 1 vs. 26 ± 2	<0.001
LPS in young	AMG517 vs. vehicle	0.9	0.2 ÷ 1.6	<0.010	4.1	<0.05	19 ± 1 vs. 26 ± 2	0.003
LPS in aged	AMG517 vs. vehicle	−1.0	−1.8 ÷ −0.2	<0.015	5.4	<0.05	19 ± 1 vs. 16 ± 1	<0.040
LPS in aged	Trpv1^−/− vs. Trpv1^+/+	−1.3	−2.4 ÷ −0.2	<0.020	5.4	<0.05	24 ± 3 vs. 19 ± 1	<0.100
CLP in aged	Trpv1^−/− vs. Trpv1^+/+	0.7	−0.5 ÷ 1.9	0.239	1.4	>0.05	20 ± 2 vs. 52 ± 11	<0.007