Noninfectious nonmalignant diseases
Fibroprolifeartive diseases are due to activated fibroblast proliferation and overproduction mainly of collagen leading to fibrosis. The basis of their pathogenesis is disturbances in the cytokine network. Some cytokines such as interleukin-4 (IL-4), tumor growth factor
), IL-1b stimulate collagen synthesis (Kahari et al. 1990; Kikuchi et al. 1995; Tiggelman et al. 1995; Sempowski et al. 1996). Interferon gamma (IFN
) exerts an exactly opposite effect — a strong inhibition of collagen synthesis by fibroblasts (Duncan and Berman 1987; Melin et al. 1989; Elias et al. 1990; Granstein et al. 1990; Kahari et al. 1990; Gillery et al. 1992; Narayanan et al. 1992; Serpier et al. 1992; Nguyen et al. 1994; Bird and Tyler 1995; Harrop et al. 1995; Sempowski et al. 1996; Chizzolini et al. 1998; Jaffe et al. 1999; Yokozeki et al. 1999; Yuan et al. 1999; Yamabe et al. 2000), by synovial cells (Daireaux et al. 1990), by myofibroblasts (Granstein et al. 1990), by chondrocytes (Reginato et al. 1993; Goldring et al. 1994), and by osteoblasts (Smith et al. 1987; Hirose et al. 1989). An important enzyme which catalyzes one of the steps in the synthesis of procollagen and its production is propyl-4-hydroxylase, which is considerably increased in fibroblasts of systemic sclerosis (SSc) patients. IFN
exerts a strong suppressing effect on this enzyme (Kawaguchi et al. 1992).