TISSUE DISTRIBUTION OF IL-10 MESSENGER-RNA IN NORMAL MICE - EVIDENCE THAT A COMPONENT OF IL-10 EXPRESSION IS T-CELL-INDEPENDENT AND B-CELL-INDEPENDENT AND INCREASED BY IRRADIATION

Murine IL-IO, initially identified as a product of Th2 CD4(+) T cell clones, is known to be produced by a variety of hematopoietic cells. The cellular and tissue expression of IL-10 in vivo is not known and could be relevant to understanding its functions. We examined in vivo, expression of IL-10 mRNA using RT-PCR in various normal and mutant mice and after irradiation. In addition, expression was studied during rejection of an i.p. injection of P815 tumor cells. Total RNA was extracted from whole organs; standard RT-PCR, semiquantitative PCR, and RNase protection assays were performed. In normal mice IL-10 mRNA was detectable in all tissues surveyed, Semiquantitative PCR allowed an estimation of the relative levels of IL-10 mRNA in tissues. IL-10 mRNA in spleen and kidney of nude mice and SCID mice was detectable in normal amounts. Expression of IL-10 mRNA was increased in spleen and kidney in a dose-dependent fashion after irradiation. During allogeneic stimulation IL-10 mRNA was increased in spleen and kidney as demonstrated by the PCR and RNase protection assays. In conclusion, IL-10 mRNA is detectable by PCR in many organs of normal mice and is largely T and B cell-independent. The increase of IL-10 mRNA in spleen and kidney during an intraperitoneal T cell response, at a time when IFN-gamma mRNA is known to be increased in the same organs, suggests a complex systemic interaction between IL-10 and other cytokines during rejection, Moreover, the ubiquitous tissue distribution and the increased levels of steady state IL-10 mRNA after irradiation suggest that this molecule plays a general role in the biology of all tissues and may explain some of the immunosuppressive effects of ionizing radiation.