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Interleukin 1 (alpha and beta) and tumour necrosis factor alpha do not regulate protein balance in skeletal muscle
P.101
PERITONEAL MACROPHAGES DOWN-REGULATE THEIR PRODUCTION OF INTERLEUKIN 1 DURING TUMOUR GROWTH. L.L. Moldawer, C. Lonnroth, K. Lundholm. Dept. of Surgery I, Sahlgrenska Hospital, Gijteborgs Universitet, Goteborg, Sweden Patients with advanced cancer frequently have a higher incidence and severity of bacterial infections which often leads to increased morbidity Interleukin 1 (IL-l) plays a central role in mediating and mortality. the host:s protein, trace mineral and nonspecific immune responses to infection. This study was undertaken to evaluate whether IL-1 production is altered in cancer disease. Adult C57/B16 mice received a transplantable MCG 101 fibrosarcoma implanted subcut. and on days 5, 7, 9 and 11, peritoneal macrophaqes were harvested and stimulated to produce IL-1 (with 10 ug/ml LPS) in vitro. Because tumour bearing mice become malnourished and malnutrition adversly affects IL-1 production, additional nontumour bearing mice had their food intake restricted so that their body weight was equal to carcass weight of tumour bearing animals (weight-paired). As tumour growth progressed, the production of IL-l by peritoneal macrophages declined. By day 11, when the tumour was 17% of body weight, IL-l production had declined 79% (p 0.01). Furthermore, this decline in IL-1 production could not be explained by coexistant malnutrition, since weight-paired nontumour bearing animals retained normal IL-l production. SDS-polyacrylamide gel electrophoresi3S and autoradiography of macrophage supernatants (intrins. labeled with incubated with antiS-methionine) IL-1 antibodies confirmed the absence of IL-l in tumour bearing mice. These findings demonstrate that peritoneal macrophages from tumour bearing mice have a defect in IL-l biosynthesis. This defect may explain the pathogenesis associated with a rapidly growing tumour.
p.102
INTERLEUKIN 1 (ALPHA AND BETA) AND TUMOUR NECROSIS FACTOR ALPHA DO NOT REGULATE PROTEIN BALANCE IN SKELETAL MUSCLE. L.L. Moldawer, J. Ghlin, G. Svaninger, K. Lundholm (Dept. Surgery I, Sahlgrenska Hosp. Goteborg) Recent studies have claimed that interleukin 1 (IL-l) increases skeletal protein degradation similar to that seen during infections. However, none of the preparations were pure and generally contained other products of activated blood monocytes. We have assessed the capability of recombinant IL-l and tumour necrosis factor alpha (TNF) to affect skeletal protein synthesis and degradation both in vitro and in vivo. Extensor digitorum longus (EDL) muscles from adult C57/B16 mice were removed and incubated at 37O in either Krebs-ring bicarb. (for degradation) or McCoys media with (14C)phenylalanine (for synthesis) with or without the addition of 900-1000 ngs of either rIL-1 alpha, r-IL-1 beta, rTNF, or partially-purified secretory products of Staph. albus-stimulated human monocytes. Similarly, equival. amounts ofrecombinant proteins or monocyte secretory products were administered in vivo and protein synthesis and degradation evaluated 2 hours later. Although partially-purified secretory products of stimulated human blood monocytes increased skeletal protein degradation both in vivo and in vitro (both p 0.05), none of the recombinant preparations had any impact on skeletal protein balance. Furthermore, a polyclonal antibody to IL-l completely eliminated the lymphoproliferative response to stimulated monocyte preparations, but failed to abrogate the increased skeletal protein degradation. We can only conclude that some other monocyte product, immunologically distinct from IL-1 and not TNF alpha must be responsible for the accelerated protein degradation seen with partially-purified human blood monocyte products.
149
PERITONEAL MACROPHAGES DOWN-REGULATE THEIR PRODUCTION OF INTERLEUKIN 1 DURING TUMOUR GROWTH. L.L. Moldawer, C. Lonnroth, K. Lundholm. Dept. of Surgery I, Sahlgrenska Hospital, Gijteborgs Universitet, Goteborg, Sweden Patients with advanced cancer frequently have a higher incidence and severity of bacterial infections which often leads to increased morbidity Interleukin 1 (IL-l) plays a central role in mediating and mortality. the host:s protein, trace mineral and nonspecific immune responses to infection. This study was undertaken to evaluate whether IL-1 production is altered in cancer disease. Adult C57/B16 mice received a transplantable MCG 101 fibrosarcoma implanted subcut. and on days 5, 7, 9 and 11, peritoneal macrophaqes were harvested and stimulated to produce IL-1 (with 10 ug/ml LPS) in vitro. Because tumour bearing mice become malnourished and malnutrition adversly affects IL-1 production, additional nontumour bearing mice had their food intake restricted so that their body weight was equal to carcass weight of tumour bearing animals (weight-paired). As tumour growth progressed, the production of IL-l by peritoneal macrophages declined. By day 11, when the tumour was 17% of body weight, IL-l production had declined 79% (p 0.01). Furthermore, this decline in IL-1 production could not be explained by coexistant malnutrition, since weight-paired nontumour bearing animals retained normal IL-l production. SDS-polyacrylamide gel electrophoresi3S and autoradiography of macrophage supernatants (intrins. labeled with incubated with antiS-methionine) IL-1 antibodies confirmed the absence of IL-l in tumour bearing mice. These findings demonstrate that peritoneal macrophages from tumour bearing mice have a defect in IL-l biosynthesis. This defect may explain the pathogenesis associated with a rapidly growing tumour.
p.102
INTERLEUKIN 1 (ALPHA AND BETA) AND TUMOUR NECROSIS FACTOR ALPHA DO NOT REGULATE PROTEIN BALANCE IN SKELETAL MUSCLE. L.L. Moldawer, J. Ghlin, G. Svaninger, K. Lundholm (Dept. Surgery I, Sahlgrenska Hosp. Goteborg) Recent studies have claimed that interleukin 1 (IL-l) increases skeletal protein degradation similar to that seen during infections. However, none of the preparations were pure and generally contained other products of activated blood monocytes. We have assessed the capability of recombinant IL-l and tumour necrosis factor alpha (TNF) to affect skeletal protein synthesis and degradation both in vitro and in vivo. Extensor digitorum longus (EDL) muscles from adult C57/B16 mice were removed and incubated at 37O in either Krebs-ring bicarb. (for degradation) or McCoys media with (14C)phenylalanine (for synthesis) with or without the addition of 900-1000 ngs of either rIL-1 alpha, r-IL-1 beta, rTNF, or partially-purified secretory products of Staph. albus-stimulated human monocytes. Similarly, equival. amounts ofrecombinant proteins or monocyte secretory products were administered in vivo and protein synthesis and degradation evaluated 2 hours later. Although partially-purified secretory products of stimulated human blood monocytes increased skeletal protein degradation both in vivo and in vitro (both p 0.05), none of the recombinant preparations had any impact on skeletal protein balance. Furthermore, a polyclonal antibody to IL-l completely eliminated the lymphoproliferative response to stimulated monocyte preparations, but failed to abrogate the increased skeletal protein degradation. We can only conclude that some other monocyte product, immunologically distinct from IL-1 and not TNF alpha must be responsible for the accelerated protein degradation seen with partially-purified human blood monocyte products.
149