Recombinant Tumor Necrosis Factor-  Chronically Administered in Rats: Lack of Cachectic Effect

Abstract

Recombinant human tumor necrosis factor-alpha (rHuTNF) was injected into rats to test its reported cachectic effects. Rats were subcutaneously injected daily at 1730 hr with either saline or rHuTNF (0.25 mg/kg body wt) for either 5 or 14 days. Daily food intakes were significantly depressed only for the first day and first two days of rHuTNF injection in animals treated for 5 days and 14 days, respectively. There were no significant differences in daily body weights among the groups. Analysis of carcass composition revealed no significant differences in percentage of lipid or protein. Liver and inguinal pad weights were not significantly different. In vitro determination of lipogenesis showed it was enhanced in the inguinal pad and depressed in the liver only after 14 days of treatment. These results demonstrate that although in vivo rHuTNF may specifically alter tissue metabolism, it does not, by itself, result in a sustained cachectic effect.

TNF-Alpha in the Locomotor System beyond Joints: High Degree of Involvement in Myositis in a Rabbit Model

“…However, there is a marked discrepancy in the literature regarding the effect of TNF-alpha on the musculature. Some studies on myoblast cell culture show that TNF-alpha administration does not have catabolic effects (e.g., [45]), and other studies documenting accumulations of inflammatory cells in skeletal muscle in response to TNF-alpha administration [4] show no decrease in skeletal muscle proteins and no signs of muscle atrophy or injury. Perhaps these discrepancies reflect a dual role of TNF-alpha where in some circumstances inflammatory cell derived TNF-alpha can play a protective role [46] and also be involved in the recovery of muscle function after traumatic injury [9] and in muscle regeneration [47].…”

The proteasome inhibitor MG132 reduces immobilization-induced skeletal muscle atrophy in mice

“…TNFα is known to increase the activity of the canonical NFκB pathway in conditions associated with muscle weakness, including sepsis, cancer, and ageing [36-39] and to cause protein degradation in cultured myotubes [5,6]. In fact, the ubiquitin-proteasome pathway has been shown to be of major importance in the catabolic signaling of TNFα leading to the breakdown of muscle protein [40].…”

Cancer cachexia

“…Effect of cachectic factors on host body weight A number of studies have demonstrated the ability of TNF to induce weight loss in experimental animals, although some workers question the ability of TNF alone to yield a sustained cachectic effect (Mullen et al, 1990). In all cases weight loss is accompanied by a marked anorexia, and the depression in food and water intake is probably responsible for the wasting effect.…”