Inhibition of interleukin-8 reduces human malignant pleural mesothelioma propagation in nude mouse model.
Malignant pleural mesothelioma (MPM), despite current therapeutic strategies, 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 the 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-2081), equally divided into three groups (IL-8 Ab, control Ab, untreated), and received IP injection of IL-8 Ab, control Ab, or no treatment, respectively, every 48 h up to 15 days. Pleural fluid and serum IL-8 levels, and tumor and body weight of mice were measured following 5, 10, and 15 days of tumor 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 tumor growth. There was a significant and direct correlation between pleural fluid IL-8 levels and tumor weight of all animals enrolled in this study (P < 0.0001, r = 0.88). We demonstrate that antibody treatment 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.
Galffy
G
G
Department of Medicine, Veterans Affairs Medical Center, Indiana University Medical Center, Indianapolis 46202, USA.
Mohammed
K A
KA
Nasreen
N
N
Ward
M J
MJ
Antony
V B
VB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001835:Body Weight; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008654:Mesothelioma / Q000097:blood / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D010996:Pleural Effusion / Q000737:chemistry; D010997:Pleural Neoplasms / Q000097:blood / Q000628:therapy*
D000911:Antibodies, Monoclonal; D016209:Interleukin-8