Potential role of immunological factors in early diagnosis of cancer cachexia in C26 tumor-bearing mice

Abstract

Cachexia is a wasting syndrome associated with high mortality in cancer patients through inducing the failure of normal metabolism and reducing the efficacy of cancer treatment. Thus, it is critically important to diagnose cancer cachexia early. To provide background data for the diagnosis of cachexia, cancer cachectic factors were characterized in the present situation, including immunological cachectic changes during cachexia progression in a cancer cachexia mouse model. Major constitution of cachexia progression is known as the stages of pre-cachexia, cachexia, and refractory cachexia. In the pre-cachexia stage, the weights of immune-related organs, including the thymus and spleen were significantly. T cell populations in spleen were markedly reduced and cachectic cytokines consistently increased in a time-dependent manner. Immunosuppression by activation of cytotoxic T-lymphocyte-associated antigen 4 was induced earlier in CD4(+) cells versus other T cell populations. Furthermore, monocyte chemoattractant protein 1 and interleukin-6 levels in the cachexia group were significantly increased at 3days from C26 cell inoculation whereas significant carcass weight loss as a classical diagnostic marker occurred at 9days from C26 cell inoculation. In conclusion, the initiation of cachectic immunological changes was observed prior to weight loss, during the pre-cachexia stage. Accordingly, these findings reveal that the monitoring of humoral and immunological factors may be more sensitive than weight loss for the initial diagnosis and treatment of cachexia.