Interleukin 3 activity in tumor-bearing hosts: decreased splenocyte production of and responsiveness to IL 3.
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.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D005354:Fibrosarcoma / Q000276:immunology*; D007377:Interleukin-3; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010835:Phytohemagglutinins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D007377:Interleukin-3; D008222:Lymphokines; D010835:Phytohemagglutinins; D003208:Concanavalin A