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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #162023

Title: ROLE OF INFLAMMATORY CYTOKINES IN A MODEL OF TURPENTINE-INDUCED CACHEXIA

Author
item SCHNEIDER, STEPHANE - UNIVERSITY OF NICE,FRANCE
item JANSSEN, IAN - TUFTS-HNRCA
item SANCHEZ, NADA - TUFTS-HNRCA
item SMITH, DONALD - TUFTS-HNRCA
item PALADUGULA, NEELINA - TUFTS-HNRCA
item CASTANEDA-SCEPPA, CARMEN - TUFTS-HNRCA
item ROUBENOFF, RONENN - MILLINNEUM PHARM INC
item VANNIER, EDOUARD - TUFTS-HNRCA

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/1/2003
Publication Date: 12/3/2003
Citation: Schneider, S.M., Janssen, I., Sanchez, N., Smith, D., Paladugula, N., Castaneda-Sceppa, C., Roubenoff, R., Vannier, E. 2003. Role of inflammatory cytokines in a model of turpentine-induced cachexia [abstract]. Nutrition Clinic of Metabolism. 17(Suppl 1):25S.

Interpretive Summary:

Technical Abstract: Subcutaneous injection of turpentine is a well-established model to study systemic inflammation. The aim of our study was to assess the effects of this chemical stress on muscle mass and on gene expression of cytokines known to control muscle mass. At day 0, 100 micro-L of turpentine were injected sc in the right hindlimb of 79 young mice deficient for the genes encoding IL-1 receptor 1 (i1), TNF receptors 1 and 2 (dt), or TNF receptor 1 and IL-1 receptor 1 (it). C57BL/6 and B6; 129 mice were controls for mice deficient for one or two genes, respectively. Body weight was recorded daily for 16 days. Solei from the homolateral (HS) and contralateral (CS) limbs to the injection, and plasma were harvested on day 16. Plasma IL-6 protein levels (ELISA), TNF-alpha and IL-1beta transcripts were measured in solei by quantitative RT-PCR (Taqman). Means (+/-SEM) were compared by ANOVA. Body weight reached a nadir on day 3, and returned to initial levels on day 9. Between days 0 and 3, the loss of body weight was less severe in "i1" mice (2.3+/-0.4%) than in C57BL/6 wild-type mice (7.2+/-0.7%; P=0.001), but was more severe in "dt" mice (7.5+/-0.7%) than in B6;129 wild-type mice (6.3+/-1.2%; P=0.02). In the wild-type groups, plasma IL-6 levels did not differ between days 0 and 16, indicating the absence of systemic inflammation had resolved. On day 16, deletion of "il" prevented HS weight loss, but had no effect on CS weight. In HS, deletion "il" or "dt" did not modify TNF-alpha and IL-1beta mRNA levels (normalized to 18S rRNA levels). In CS, deletion "dt" had no effect on these transcript levels, suggesting that TNF-alpha is not a major inducer of TNF-alpha and IL-1beta synthesis. In CS, deletion "il" reduced transcript levels for TNF-alpha (-46%) and IL-1beta (-91%). In the absence of systemic inflammation, locally produced IL-1beta plays a major role in soleus atrophy and in expression of the TNF-alpha and IL-1beta genes.