IN-VITRO EXCESS AMMONIA PRODUCTION IN HUMAN MYELOMA CELL-LINES

It is well known that cases with multiple myeloma reveal various clini cal manifestations such as pancytopenia, hyperproteinemia, renal dysfu nction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary t ype hyperamylasemia and elevated serum C-reactive protein (CRP) concen tration, have been reported. The elevation of CRP is thought to be rel ated to interleukin-6 (IL-6) production by myeloma cells, because of i dentification of IL-6 as an autocrine and/or paracrine growth factor f or myeloma cells. More recently, there have been several reports of ca ses with myeloma associated with hyperammonemia. This hyperammonemia i s not considered to be due to liver dysfunction, because in most of th ese cases tests revealed normal hepatic function, and some cases showe d different patterns of serum amino acid distribution than that associ ated with hepatic failure. However, there have been no apparent observ ations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently esta blished from a myeloma case associated with hyperammonemia. These lili es were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological c ell lines or the HepG2 human hepatic carcinoma cell line. Although att empts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase ch ain reaction assay failed to detect any differences between these myel oma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifest ations is discussed.