(A) WT and Il1r1loxP/loxP animals exhibit significant and comparable serum IL-6 elevations 2 hrs after IL-1α injections (1 μg, i.p.), as compared to vehicle treated controls (two-way ANOVA, P < 0.0001 for treatment, genotype and their interaction, followed by post hoc Tukey’s multiple comparison tests, *** = P < 0.0001). IL-1α induced IL-6 elevations were found to be IL-1R1 dependent, as revealed by a lack of response in Il1r1-/- animals. N = 4-6/group for all assays. (B) Excision of floxed Il1r1 alleles by global Cre recombinase expression in Il1r1loxP/loxP mice attenuates the ability of IL-1α treatment to increase serum IL-6 expression. No increases in IL-6 expression were found in IL-1α treated Il1r1loxP/loxP:CMV Cre or Il1r1-/- mice (one way ANOVA, P < 0.0001, followed by post hoc Tukey’s multiple comparison tests, *** = P < 0.0001) N = 5-7/group for all assays.