High levels of IL-4 and IL-10 mRNA and low levels of IL-2, IL-9 and IFN-gamma mRNA in MuLV-induced lymphomas

The expression of cytokines may influence the development of lymphoma in re trovirally infected animals in at least two ways: (1) cytokines in the tumo r environment may stimulate the proliferation of tumor cells and/or (2) cyt okines in the tumor environment may diminish the cell-mediated antitumor im mune response. To evaluate these possibilities, a semiquantitative RT-PCR a pproach was utilized to permit a broad screening of cytokine mRNAs in a lar ge number of tissue samples. Examination of MuLV-induced end-stage lymphoma s revealed the absence of mRNA for cytokines known to stimulate the prolife ration of T cells (i.e., IL-2, IL-9), the absence of mRNA for cytokines kno wn to enhance cell-mediated antitumor immune responses (i.e., IL-2, IFN gam ma), and the presence of mRNA for cytokines known to diminish such response s (i.e., IL-4, IL-10). Similar patterns of cytokine mRNA expression were de tected in tumor-derived cell lines. Spleen and thymus from animals collecte d longitudinally during infection and from age-matched uninfected mice also demonstrated a similar pattern, except that IFN gamma mRNA was readily det ectable. These findings do not support the hypothesis that the developing t umor depends on cytokines to provide proliferative signals. The findings su ggest that cytokines in the immediate environment of the lymphoma support t umor development by acting to diminish an effective antitumor immune respon se. (C) 1999 Academic Press.