Obesity, low-grade inflammation, and inflammatory response to immune challenge modulate willingness to expend effort for reward

Background: Inflammation is increasingly considered a vulnerability factor for deficits in reward motivation. It remains unclear if such motivational changes differ between acute and chronic low-grade inflammation. Given obesity’s link to chronic low-grade inflammation, the present study tested the effect of obesity and the impact of low-grade inflammation (elevated CRP concentrations), as well as the effect of acute inflammation (experimental immune challenge using lipopolysaccharide), on motivation for a monetary reward. Moreover, the wear-and-tear induced by chronic inflammation could amplify motivational changes induced by immune challenge. Thus, we also tested the hypotheses that acute inflammation is associated with more strongly altered reward motivation for individuals with higher low-grade inflammation, and for obese than normal-weight individuals. Methods: Healthy obese (n=14) and normal-weight (n=21) young adults were intravenously injected with a bacterial endotoxin (lipopolysaccharide, LPS [0.8 ng/kg body weight]) to trigger an acute inflammatory response, and placebo (saline) in a counterbalanced, randomized, crossover design. The Effort Expenditure for Reward Task (EEfRT) was administered 2 hours following each injection to assess reward motivation. Blood was sampled pre- and post-injection to quantify concentrations of inflammatory proteins (interleukin [IL]-6 and C-reactive protein [CRP]). Results: Obese participants and higher low-grade inflammation (baseline CRP) was associated with overall reduced motivation to expend effort for reward in the placebo condition. An interaction with reward magnitude was observed, so that this effect occurred at smaller reward values, but not when reward values increased. LPS-induced inflammatory responses (IL-6 concentrations during EEfRT) were associated with a weaker influence of reward magnitude on increasing effort. Unexpectedly, we did not detect the amplification effect of obesity and its associated low-grade inflammation on the ability of lipopolysaccharide to modulate reward motivation. Conclusions: Lipopolysaccharide-induced and low-grade inflammation alter how effort is allocated towards reward, with low-grade inflammation increasing the reward threshold for exerting effort and acute inflammation dampening reward sensitivity. This study offers a nuanced understanding of inflammatory processes underlying alterations in reward motivation.