**2. Mechanisms of IL-6 induced muscle catabolism**

In one study, to date, IL-6 has been shown to reduce basal and eccentric exercise induced protein synthesis by generally well accepted mechanisms [10].

One mechanism by which IL-6 decreases muscle mass is by activating the STAT 3 pathway which causes muscle protein breakdown to acute phase proteins. An acute phase protein derived from skeletal muscle that is synthesized upon IL-6 binding in skeletal muscle and activation of the STAT 3 pathway is fibrinogen. This was reported in an experimental animal model of cancer cachexia [2]. In a subsequent study this group also reported that blocking the JAK/STAT 3 pathway inhibited skeletal muscle wasting [3]. Therefore, this is a way that IL-6 induces muscle protein breakdown also known as proteolysis.

Another mechanism described in the literature [11] is autophagy where the cells in essence eat themselves. This would be considered a second mechanism by which proteolysis is induced by IL-6.

A third mechanism by which IL-6 can induce protein breakdown is by activation of atrogin 1 (MAFBX) [12].
