ROLE OF INTERLEUKIN-10 IN THE LUNG RESPONSE TO SILICA IN MICE

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cy tokines contributes to the induc tion of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10),an anti-inflammatory cytokine, in the development of silicosis. In a mous e model of inflammatory lung reaction induced by intratracheal instill ation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 prot ein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increa sed when compared with controls. After in vitro lipopolysaccharide (LP S) stimulation (1 mu g/ml), BAL cells obtained from silica-treated ani mals produced significantly more IL-10 protein and mRNA than cells obt ained from control animals. To examine the role of IL-10 in the lung r eaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of t he inflammatory response (lactate dehydrogenase [LDH], protein and num ber of inflammatory cells in BAL) was significantly greater in IL-10-d eficient animals than in the wild type. In contrast, the fibrotic resp onse, evaluated by measuring lung hydroxyproline content and by histop athologic analysis 30 days after silica, was significantly less import ant in IL-10-deficient than in wild-type mice. Together, these data su ggest that increased IL-10 synthesis induced by silica can limit the a mplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.