Inhibition of interleukin-8 reduces human malignant pleural mesothelioma propagation in nude mouse model

Malignant pleural mesothelioma (MPM), despite current therapeutic strategie s, is still an aggressive tumor with a very poor prognosis. Interleukin-8 ( IL-8), a proinflammatory and angiogenic cytokine, has an important role in tumor-related neovascularization. IL-8 has also been described to function as an autocrine growth factor. The purpose of this study was to evaluate th e effect of IL-8 antibody (IL-8 Ab) on progression of MPM in vivo. Athymic nude mice (n = 65) were injected intrapleurally with human MPM cells (CRL-2 081), equally divided into three groups (IL-8 Ab, control Ab, untreated), a nd received IP injection of IL-8 Ab, control Ab, or no treatment, respectiv ely, every 48 h up to 15 days. Pleural fluid and serum IL-8 levels, and tum or and body weight of mice were measured following 5, 10, and 15 days of tu mor injection. We found that both pleural fluid and serum IL-8 levels were significantly (P<0.0001) lower in mice that received IL-8 Ab when compared to the other groups. In this group, lower IL-8 levels were associated with a decreased rate of turner growth. There was a significant and direct corre lation between pleural fluid IL-8 levels and tumor weight of all animals en rolled in this study (P < 0.0001, r = 0.88). We demonstrate that antibody t reatment against IL-8 decreased human MPM progression. Our results suggest that treatments targeting the decrease of MPM-associated IL-8 levels or the effects of this protein may inhibit mesothelioma growth.