Regulation of food intake and hepatic protein synthesis by recombinant-derived cytokines

Abstract

During inflammation, activated monocytes and lymphocytes synthesize and release many soluble protein mediators, such as interleukin (IL) 1, tumor necrosis factor-alpha, and IL-2. It is presently unclear which cytokines, if any, contribute to the anorexia and hepatic protein changes frequently seen during inflammation. To evaluate their potential role, food intake and liver and plasma protein synthesis were determined in both endotoxin-sensitive C57Bl/6j mice and endotoxin-resistant C3H/HeJ mice given either crude secretory products of Staphylococcus albus-stimulated human blood monocytes or murine recombinant IL-1-alpha, human recombinant IL-1-alpha or -beta, human recombinant tumor necrosis factor-alpha, or human IL-2. When given intraperitoneally to healthy animals, 2,000 lymphocyte-activating factor U/day of secretory products of activated human blood monocytes or recombinant murine IL-1-alpha depressed spontaneous food intake by 42 and 53%, respectively. Human IL-1-alpha and -beta and human tumor necrosis factor-alpha produced smaller reductions in food intake. In contrast, human IL-2, when given in equimolar quantities, had no appreciable effect on food intake or body weight. Administration of crude secretory products of activated blood monocytes, recombinant IL-1, or tumor necrosis factor-alpha increased liver weight, protein, and RNA content. In addition, plasma protein synthesis was significantly increased, as were serum amyloid P concentrations. Administration of recombinant tumor necrosis factor-alpha resulted in IL-1 production by peritoneal adherent cells. However, IL-2 had no effect on any hepatic parameter.

Elevation of cytokine levels in cachectic patients with prostate carcinoma

“…33,34 However, neutralization of IL-1 by antibodies, 35 administration of an IL-1 receptor antagonist, 36 and transfection of an IL-1 receptor antagonist 37 failed to prevent cachexia in mice. The objectives of the current study were to determine the levels of TNF␣, IL-1␤, IL-6, and IL-8 in patients with CaP and to determine whether higher levels of these cytokines are associated with cachexia.…”

Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect

“…A number of studies have been conducted to explore the factors responsible for this cachexia, and it has been revealed that elevated blood levels of tumour necrosis factor α (TNF-α), interleukin 1 (II-1), IL-6, IL-11, γ-interferon, leukaemia inhibitory factor or 24 kDa proteoglycan may induce cachexia (Beutler et al, 1986;Moldawer et al, 1988;Metcalf et al, 1990;Matthys et al, 1991;Strassmann et al, 1992a;Ohsumi et al, 1994;Todorov et al, 1996). One of these factors, IL-6, is a pleiotropic cytokine physiologically involved in the differentiation of myeloid and neuronal cells, and pathologically involved in the early host response to infection and injury (Kishimoto, 1989), in the proliferation of myeloma (Kawano et al, 1988), urological cancer cells (Miki et al, 1989;Okamoto et al, 1997a,b) and possibly breast cancer cells (Chiu et al, 1996), and in the development of hypercalcaemia and osteolytic metastases (De La Mata et al, 1995).…”

Proinflammatory cytokines, nutritional support, and the cachexia syndrome

“…111 The that accompanies acute inflammation. Not only are antianabolic properties of IL-1 and IL-6 could thus these cytokines catabolic when administered in vivo to be mediated in part through alterations in the IGF-1 animals, 40,65,97,102 but blocking an IL-1 or IL-6 response pathway. after a turpentine abscess reduces the carcass protein Similarly, in rats treated with RU38486 and TNFlosses that occur.…”

“…25 In fact, the majority of increases in whole body protein synthesis to healthy animals can reproduce the acute phase responses observed in acute inflammation. 28,40 This could be explained by increases in liver protein synthesis. Moreover, the livers of these animals were apoverlapping biological response is due in part to the fact that under in vivo conditions, TNF-a can induce proximately 10 -20% larger with 10 -20% more protein than the livers of comparably fasted animals.…”

“…30,31 receptor that then complexes with gp 130. By sharing a single signal transduction pathway, all these memIn general, although the protein response to inflammation, regardless of its source, is one of inbers of the IL-6 super family share with IL-6 the ability to induce an acute phase response ( inflammation often elicits a cytokine cascade in which a Summarized from Moldawer et al, 40 Espat et al, 47 Moldawer et al, 77 and unpublished data of Moldawer et al…”