Anti-inflammatory Effect of Spontaneous Lymphoma in SJL/J Mice2

Abstract

Histiocytic lymphomas develop spontaneously in about 80% of SJL/J mice between the ages of 8 and 14 months. These animals were used for the determination of whether spontaneously arising cancers compromise monocyte function similar to the monocyte defects described during growth of transplanted tumors. SJL/J mice with tumors accumulated significantly fewer macrophages than did age-matched animals without tumors either on sc implanted filters or in peritoneal exudates induced by phytohemagglutinin. There was no corresponding defect in polymorphonuclear neutrophil responses. Whereas no apparent correlation existed between tumor size and degree of inhibition, animals without demonstrable tumors had no inflammatory defects. Aging did not alter the inflammatory response to implanted filters but increased both the resident peritoneal macrophage population and the total macrophage yield to phytohemagglutinin provocation. When given transplants of histiocytic lymphomas, young SJL/J mice developed similar inflammatory defects. This study represents the first demonstration that spontaneous tumors, in addition to transplanted tumors, produce abnormalities in monocyte inflammatory responses.

Macrophage infiltration and tumor progression

“…During this period, the accumulation of macrophages within the tumor slows despite tumor growth causing a rise in the T/M ratio (Normann and Cornelius, 1978). this phase often is associated with a systemic impairment of macrophage inflammatory responses by both autochthonous and transplanted tumors (Bernstein et al, 1972;Fauve et al, 1974;Snyderman et al, 1976;Normann & Sorkin, 1976;Normann et al, 1979b;1981a.…”

“…A small, emerging tumor might inhibit macrophage accumulation locally without impairing all monocytes of the body. It may be significant that the 2 spontaneously arising tumors in which anti-inflammation was Normann et al 1979bNormann et al , 1981aNormann et al , I984, 1985aNolibe et al 1980. most consistently observed were of hematopoetic origin wherein the circulating blood might be considered the local tumor compartment. Second, we know that the anti-inflammatory phenomenon is biphasic with an early transient component that might be easily missed.…”

Host-Tumor Interactions in the SJL Lymphoma Model

“…Moreover, Normann et af. [77] have shown that primary, as well as serially transplanted RCS, have a profound anti-inflammatory effect as measured by inhibition of macrophage accumulation.…”

Effects of tumor growth on host defenses

“…In 1980, however, we demonstrated that MCI activity was present in primary mammary adenocarcinomas arising in C3H mice which carried the murine mammary tumor virus (MMTV) (40). A year earlier, Normann and his colleagues had also demonstrated anti-inflammatory activity associated with spontaneous histiocytic lymphomas in SJL/J mice (20). In our 1980 study we showed that a low molecular weight ultrafiltrate (<25,000 daltons), prepared from as few as 2 x 105 spontaneous mammary tumor cells, inhibited the intraperitoneal accumulation of macrophages in response to PHA.…”