Interleukin Generation in Experimental Colon Cancer of Rats: Effects of Tumor Growth and Tumor Therapy2

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Abstract
The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P<.01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P<.01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P<.01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.