CACHEXIA AND THE ACUTE-PHASE PROTEIN RESPONSE IN INFLAMMATION ARE REGULATED BY INTERLEUKIN-6

Cachexia and the acute-phase response are common manifestations of inf lammation and are presumed to be the product of increased synthesis an d release of cytokines, including tumor necrosis factor (TNF), interle ukin-1 (IL-1) and interleukin-6 (IL-6). IL-1 receptor blockade has bee n previously shown to attenuate the weight loss, anorexia and acute-ph ase protein responses associated with a turpentine abscess. However, I L-1 receptor blockade was also associated with a reduced plasma IL-6 r esponse, suggesting that the benefit achieved by IL-1 receptor blockad e 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, C57B L/6 mice were passively immunized with either a monoclonal anti-IL-6 a ntibody (20F3), an anti-IL-I type I receptor monoclonal antibody (35F5 ), a non-immune rat IgG, or a combined therapy of 35F5 and 20F3, befor e receiving a sterile turpentine abscess. IL-6 or IL-1 receptor blocka de equally spared body weight and food intake. Compared to IL-1 recept or blockade, passive immunization against IL-6 further reduced the hep atic acute-phase protein response, as represented by serum amyloid P a nd complement 3. Combined blockade of IL-6 and IL-1 receptor did not r esult in a further sparing of body weights or improvement of food inta ke. These results confirm that IL-1 contributes to host cachexia and t he acute-phase response following a turpentine abscess, but also show that these actions are dependent upon an IL-6 response. We conclude th at the influence of IL-1 on cachexia and the acute-phase response is m ediated, at least in part, through IL-6 and, thus. IL-6 may play a piv otal role in the cachexia and acute-phase response to inflammation.