Virlaza® Efficiently Inhibited LPS-induced
Acute Lung Injury
Acute Lung Injury
Maysa Alves Rodrigues Brandao-Rangel1*, Dobroslav Melamed2*, Anamei Silva-Reis1, Boris Brill2, Manoel Carneiro Oliveira-Junior3, Edilson de Souza Carvalho3, Razi Ronen2, Rodolfo P Vieira1,2,3,4
1- Federal University of São Paulo (UNIFESP), Laboratory of Pulmonary and Execise Immunology, Rua Talim 330, São José
dos Campos – SP, Brazil, 12231-280.
2- Libipharm, Research and Development Department, Ben Gurion 70, Rechovot, Israel, 7639461.
3- Evangelical University of Goias (Unievangelica), Post-graduate Program in Human Movement and Rehabilitation and in
Pharmaceutical Sciences, Avenida Universitaria kmKm 3,5, Anápolis – GO, Brazil, 75083-515.
4- Universidade Brasil, Post-graduate Program in Bioengineering, Rua Carolina Fonseca 235, São Paulo – SP, Brazil, 08230-
030.
Acute lung injury (ALI) presents a high rate of mortality and morbidity. Pulmonary and systemic inflammation plays a
key role in the prognosis of patients with ALI. Lipopolysaccharide (LPS)-induced ALI is a classical model to study the
pathophysiology as well to test new treatment of ALI.
In the present study, Escherichia coli LPS (026:B6; L3755, Sigma Aldrich, St. Louis, MO, USA) were administered intra-peritoneally (i.p.) in male C57Bl/6 mice to induce ALI. Control (n = 12), Virlaza (50ul intra-nasally; n = 12), LPS (100ug i.p.; n = 12) and LPS + Virlaza (100ug i.p. +50ul intra-nasally; n = 12) were studied. The results demonstrated that Virlaza significantly inhibited LPS-induced lung inflammation, notably through reduced number of total leukocytes (p<0.01), neutrophils (p<0.01), lymphocytes (p<0.01) and macrophages (p<0.01) in the bronchoalveolar lavage (BAL), while also reduced the BAL levels of IL-1beta (p<0.01), IL-6 (<0.01), CXCL1/KC (p<0.01), IL-17 (p<0.01) and TNF-alpha (p<0.01).
On the other side, Virlaza increased the levels of anti-inflammatory cytokine IL-10 (p<0.001). Such results were confirmed by quantitative histological analysis, since Virlaza reduced the accumulation of neutrophils (p<0.05), lymphocytes (p<0.05) and macrophages (p<0.05) in the lung parenchyma. In addition, Virlaza also inhibited LPS-induced systemic inflammation, as denoted by reduced number of total leukocytes (p<0.01), neutrophils (p<0.001), lymphocytes (p<0.05), and monocytes (p<0.01). Of note, Virlaza also reduced the serum levels of IL-1beta (p<0.05), IL-6 (<0.001), CXCL1/KC (p<0.05), IL-17 (p<0.001) and TNF-alpha (p<0.001), while increased the levels of IL-10 (p<0.001).
Thus, we conclude that Virlaza possesses potent pulmonary and systemic anti-inflammatory effects against bacterial infection, which deserves further clinical trials to confirm such pre-clinical findings.
1- Federal University of São Paulo (UNIFESP), Laboratory of Pulmonary and Execise Immunology, Rua Talim 330, São José
dos Campos – SP, Brazil, 12231-280.
2- Libipharm, Research and Development Department, Ben Gurion 70, Rechovot, Israel, 7639461.
3- Evangelical University of Goias (Unievangelica), Post-graduate Program in Human Movement and Rehabilitation and in
Pharmaceutical Sciences, Avenida Universitaria kmKm 3,5, Anápolis – GO, Brazil, 75083-515.
4- Universidade Brasil, Post-graduate Program in Bioengineering, Rua Carolina Fonseca 235, São Paulo – SP, Brazil, 08230-
030.
Acute lung injury (ALI) presents a high rate of mortality and morbidity. Pulmonary and systemic inflammation plays a
key role in the prognosis of patients with ALI. Lipopolysaccharide (LPS)-induced ALI is a classical model to study the
pathophysiology as well to test new treatment of ALI.
In the present study, Escherichia coli LPS (026:B6; L3755, Sigma Aldrich, St. Louis, MO, USA) were administered intra-peritoneally (i.p.) in male C57Bl/6 mice to induce ALI. Control (n = 12), Virlaza (50ul intra-nasally; n = 12), LPS (100ug i.p.; n = 12) and LPS + Virlaza (100ug i.p. +50ul intra-nasally; n = 12) were studied. The results demonstrated that Virlaza significantly inhibited LPS-induced lung inflammation, notably through reduced number of total leukocytes (p<0.01), neutrophils (p<0.01), lymphocytes (p<0.01) and macrophages (p<0.01) in the bronchoalveolar lavage (BAL), while also reduced the BAL levels of IL-1beta (p<0.01), IL-6 (<0.01), CXCL1/KC (p<0.01), IL-17 (p<0.01) and TNF-alpha (p<0.01).
On the other side, Virlaza increased the levels of anti-inflammatory cytokine IL-10 (p<0.001). Such results were confirmed by quantitative histological analysis, since Virlaza reduced the accumulation of neutrophils (p<0.05), lymphocytes (p<0.05) and macrophages (p<0.05) in the lung parenchyma. In addition, Virlaza also inhibited LPS-induced systemic inflammation, as denoted by reduced number of total leukocytes (p<0.01), neutrophils (p<0.001), lymphocytes (p<0.05), and monocytes (p<0.01). Of note, Virlaza also reduced the serum levels of IL-1beta (p<0.05), IL-6 (<0.001), CXCL1/KC (p<0.05), IL-17 (p<0.001) and TNF-alpha (p<0.001), while increased the levels of IL-10 (p<0.001).
Thus, we conclude that Virlaza possesses potent pulmonary and systemic anti-inflammatory effects against bacterial infection, which deserves further clinical trials to confirm such pre-clinical findings.
Development and research of the company "LibiPharm" - "LibiPharm" Israel.
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