INTERLEUKIN-6 OVEREXPRESSION CANNOT GENERATE SERIOUS DISORDERS IN SEVERE COMBINED IMMUNODEFICIENCY MICE

C57BL16 human interleukin-6 (IL-6) transgenic mice develop mesangial p roliferative glomerulonephritis with massive IgG1 plasmacytosis and di e of renal failure in early life. To test whether the IL-6 overexpress ion could cause development of mesangial proliferative glomerulonephri tis without plasmacytosis or promote proliferation of immature B cells that have not undergone immunoglobulin gene rearrangement, the IL-6 t ransgene was introduced into mice with severe combined immunodeficienc y (SCID). In the immunocompetent Littermate IL-6 transgenic mice, ther e were various symptoms such as plasmacytosis, nephropathy, anemia, an d thrombocytosis, accompanied by marked increases in serum IL-6 levels as they aged. All these mice died by 25 weeks of age. In contrast, th e SCID-IL-6 transgenic mice had no such abnormalities, except certain hematological changes, although the transgene was expressed in various tissues. In these mice, the serum IL-6 levels were 10- to 15-fold hig her than those in the nontransgenic mice, and they remained constant t hroughout their lives. Furthermore, there were no signs of lymphoid de velopment. This study demonstrates that deregulation of IL-6 expressio n does not stimulate cell growth or differentiation of immature B cell s, and thus does not result in plasmacytosis and age-related increases in IL-6 production, and also does not generate mesangial proliferativ e glomerulonephritis. (C) 1997 Academic Press.