Cachexia and the acute-phase protein response in inflammation are regulated by interleukin-6

Abstract

Cachexia and the acute‐phase response are common manifestations of inflammation and are presumed to be the product of increased synthesis and release of cytokines, including tumor necrosis factor (TNF), interleukin‐1 (IL‐1) and interleukin‐6 (IL‐6). IL‐1 receptor blockade has been previously shown to attenuate the weight loss, anorexia and acute‐phase protein responses associated with a turpentine abscess. However, IL‐1 receptor blockade was also associated with a reduced plasma IL‐6 response, suggesting that the benefit achieved by IL‐1 receptor blockade may be mediated by reduced systemic IL‐6 production. To gain a better understanding of the role of IL‐6 in this model of inflammation, C57BL/6 mice were passively immunized with either a monoclonal anti‐IL‐6 antibody (20F3), an anti‐IL‐1 type I receptor monoclonal antibody (35F5), a non‐immune rat IgG, or a combined therapy of 35F5 and 20F3, before receiving a sterile turpentine abscess. IL‐6 or IL‐1 receptor blockade equally spared body weight and food intake. Compared to IL‐1 receptor blockade, passive immunization against IL‐6 further reduced the hepatic acute‐phase protein response, as represented by serum amyloid P and complement 3. Combined blockade of IL‐6 and IL‐1 receptor did not result in a further sparing of body weights or improvement of food intake. These results confirm that IL‐1 contributes to host cachexia and the acute‐phase response following a turpentine abscess, but also show that these actions are dependent upon an IL‐6 response. We onclude that the influence of IL‐1 on cachexia and the acute‐phase response is mediated, at least in part, through IL‐6 and, thus, IL‐6 may play a pivotal role in the cachexia and acute‐phase response to inflammation.