History of phase-advancing light conditions exacerbates lipopolysaccharide (lPS)–induced inflammatory cytokine transcript level. Male mice received either no injection (n = 8/gp) or 50 ng/ml lPS stereotaxic brain injections (n = 12/gp) after a history of exposure to either control (constant 12:12 light cycle), advanced (4 weekly 6-h advanced), or delayed (4 weekly 6-h delayed) light cycles. (A) Mean and individual baseline mRNA transcript levels were compared across noninjected mice exposed to all 3 conditions. Interleukin-6 (IL-6) and IL-1β did not differ among groups at baseline, but both tumor necrosis factor-α (TNF-α) and IL-10 were higher in the delayed group than in the unshifted controls. (B) After elicitation by lPS injection, the IL-6 transcript level increased significantly in the phase-advanced group compared with controls. IL-10 was significantly increased in delayed versus controls. IL-1β and TNF-α did not differ among groups. (C) Ratios of pro- to anti-inflammatory cytokine transcript levels showed phase-advanced mice had a dysregulated response in all 3 comparisons: IL-6:IL-10, IL-1β:IL-10, and TNF-α:IL-10. p values reflect post hoc comparisons against the relevant control group: *p ≤ 0.05; **p ≤ 0.001; ***p ≤ 0.0001.