Immune challenge-induced oxidative damage may be mitigated by biliverdin

Abstract

An effective immune response results in the elimination of pathogens, but this immunological benefit may be accompanied by increased levels of oxidative damage. However, organisms have evolved mechanisms to mitigate the extent of such oxidative damage, including the production and mobilization of antioxidants. One potential mechanism of mitigating immune-challenge-induced changes in oxidative physiology is increasing biliverdin production. Biliverdin is chemically an antioxidant, but within-tissue correlations between biliverdin concentration and oxidative damage have never been directly examined. To test how biliverdin tissue concentrations are associated with physiological responses to an immune challenge, we exposed northern bobwhite quail (Colinus virginianus) to one of four treatments: an injection of a non-pathogenic antigen, (i.e., either lipopolysaccharide or phytohaemagglutinin), a control injection of phosphate buffered saline, or a sham procedure with no injection. Twenty-four hours later, we quantified oxidative damage and triglyceride concentration in the plasma, and biliverdin concentration in the plasma, liver, and spleen. We found that both types of immune challenge increased oxidative damage relative to both non-injected and sham-injected controls, but treatment had no effects on any other metric. However, across all birds, oxidative damage and biliverdin concentration in the plasma were negatively correlated, which is consistent with a localized antioxidant function of biliverdin. Additionally, we uncovered multiple links between biliverdin concentration, change in mass during the immune challenge, and triglyceride levels, suggesting that pathways associated with biliverdin production may also be associated with aspects of nutrient mobilization. Future experiments that manipulate biliverdin levels or oxidative damage directly could establish a systemic antioxidant function or elucidate important physiological impacts on body mass maintenance and triglyceride storage, mobilization, or transport.