Adiponectin in inflammatory and immune-mediated diseases

Circulating levels of adiponectin (APN) are reduced in obesity and associated comorbidities, with inflammation playing an important role in downregulating APN production. In contrast to obesity and metabolic disease, elevated systemic and local levels of APN are present in patients with inflammatory and immune-mediated diseases, including autoimmune and pulmonary conditions, heart and kidney failure, viral hepatitis, organ transplantation and perhaps critical illness. A positive association between inflammation and APN is usually reported in inflammatory/immune pathologies, in contrast with the negative correlation typical of metabolic disease. This review discusses the role of APN in modulation of inflammation and immunity and the potential mechanisms leading to increased levels of APN in inflammatory/immune diseases, including modification of adipose tissue physiology; relative contribution of different tissues and adipose depots; hormonal, pharmacological, nutritional and life style factors; the potential contribution of the microbiota as well as the role of altered APN clearance and release from T-cadherin-associated tissue reservoirs. Potential reasons for some of the apparently contradictory findings on the role of APN as a modulator of immunity and inflammation are also discussed, including a comparison of types of recombinant APN used for in vitro studies and strain-dependent differences in the phenotype of APN KO mice.