Interleukin 3 activity in tumor-bearing hosts: decreased splenocyte production of and responsiveness to IL 3.

Abstract

A kinetic study assessing the relationship between tumor growth and the ability of BALB/c mouse splenocytes to produce Interleukin 3 (IL 3) indicated a concomitant decrease in IL 3 activity with tumor growth. Tumor-bearing host (TBH) splenocytes produced 600 pmoles/hr/10(8) cells of IL 3 activity at Day 0 but only 62 pmoles/hr/10(8) cells by Day 28 post tumor cell inoculation. Nylon wool fractionation (to remove adherent suppressor cells) did not restore IL 3 activity. Addition of purified IL 3 to mitogen proliferation assays showed that IL 3 alone was mitogenic for normal host but not TBH splenocytes. In concert with concanavalin A (Con A) and phytohemagglutinin, IL 3 augmented in vitro normal host splenocyte responsiveness but significantly further suppressed it in the TBH. An absorption assay indicated that fresh cells had acceptors to remove IL 3 from supernatants. Con A-induced normal or TBH blast cells lost their ability to absorb IL 3. Intravenous inoculation of purified IL 3 into normal and TBH resulted in further suppression of TBH splenocyte mitogen-induced blastogenesis. The exacerbation of TBH spleen cell reactivity by IL 3 may be due to a tumor-induced feedback inhibition mechanism further suppressing cellular differentiation critical to cytotoxic T lymphocyte maturation.