Influence of the ward colon tumor on the innate and endotoxin-induced inflammatory response of the rat.

Cachexia, a depressed immune function, and an increased infection rate are recurring problems for cancer patients; the response of the host to an infection may also be increased. We have reported that the transplantable Ward colon tumor (WCT) enhanced the lethality of endotoxin (lipopolysaccharide [LPS]) to the host. The mechanism of this increased LPS lethality and the effect of the presence of the WCT on the host inflammatory response, however, have not been reported. The effect of a transplantable WCT on the innate and endotoxin-induced inflammatory response of rats was, therefore, investigated. The innate inflammatory response was investigated in two ways. First, the formation of a granuloma around a sterile string implanted subcutaneously for 6 days was determined. Second, the effect of tumor presence on the trafficking of leukocytes to a sponge implanted subcutaneously for 2 or 6 days was determined. The tumor decreased the foreign body granuloma formation around a sterile string. The presence of the WCT also significantly blunted the increase of lymphocytes that migrated to the sponge area at 6 days. There was no significant effect of the WCT, however, on the migration of neutrophils, monocytes, or eosinophils to the implanted sponge. The leukocyte distribution of the peripheral blood was not affected by the presence of the WCT or implantation of a sterile string or sponge. To determine the effect of the presence of the WCT on the response of the host to an infection, rats were given LPS (5 mg/kg, i.p.) and the alanine amino transferase (ALT) of plasma and inducible isoforms of nitric oxide synthase (NOS2) protein content of liver, spleen, and terminal ileum was determined. The LPS challenge resulted in an increase in plasma ALT concentrations and NOS2 protein content of liver and spleen, but not the terminal ileum of WCT rats. This elevation in WCT rats confirms that the enhanced LPS-related toxicity in WCT rats was related to an increased liver toxicity. The increased toxicity may be related to an increase in the nitric oxide synthesis of the liver. These results suggest that the WCT, and possibly other tumors, will reduce the ability of the host to respond to a foreign body. If this were an infection, the host would be more likely to succumb to the resulting inflammatory mediators. Further evaluations of the lymphocyte subsets and cytokines in the sponge exudate will be required to completely understand this response.