CYTOKINES AND CACHEXIA

Prolonged production of cytokines associated with cancer and chronic i nfections, and other long-term immune reactions is increasingly recogn ized as a main causal factor of the often severe signs and symptoms th at accompany these diseases: weight loss, anorexia, and metabolic brea kdown termed cachexia. The cytokine that initially was held responsibl e for causing these changes was tumor necrosis factor (TNF). However, from various studies it has become clear that the action of TNF can on ly be understood in the context of simultaneous presence of other cyto kines, some of which have activities that are at the least equally imp ortant as TNF in bringing about cachexia. This review summarizes the e xperimental evidence for the involvement of cytokines in the pathogene sis of cachexia. Indirect evidence comes from the observation that cac hexia can be induced in animals by repeated injections of cytokines or by inoculation of cytokine-producing cells. Thus, cachexia has been d escribed in mice inoculated with tumor cells carrying and expressing g enes for either TNF, interleukin-6 (IL-6), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and interferon-gamma (IFN-ga mma). More direct evidence is provided by the observations that cachex ia in experimental animal models can be mitigated by administration of specific antagonists of cytokines. These latter type of studies revea led that cachexia can rarely, if ever, be attributed to one single cyt okine but rather to a set of cytokines that work in concert in cachexi a. A pool of anticytokine antibodies or other cytokine inhibitors migh t, therefore, be considered as a potential intervention for the treatm ent of cachectic patients, but this approach may induce immunosuppress ion, and, therefore, danger exists that such treatment may benefit the infectious agent or tumor. (C) Elsevier Science Inc. 1997.