Enhanced Resistance against Influenza Virus by Treatment with Dietary Supplement d-Lenolate in Neutropenic Mice Induced by Cyclophosphamide

Relationship between depression of early protection against influenza virus infection and the decrease in the number of peripheral polymorphonuclear leukocytes (PMN) in cyclophosphamide (CY)-treated mice was investigated using d-Lenolate (Lenolate), which had been shown to exert a potent restorative effect on leukocytopenia in immuno-compromised hosts. Following intranasal inoculation with influenza virus (2.0 x 10 PFU) into untreated mice, the pulmonary virus titer progressively increased during 3 days and decreased gradually from the day 7 after infection. The treatment of mice with CY 2 days before infection markedly enhanced the pulmonary virus multiplication from the early phase of infection, and the higher virus titer was maintained thereafter. When mice were given Lenolate after CY-treatment, virus titers from the early to late phases of infection were lower than those in CY-treated controls not given Lenolate. The number of peripheral PMN in CY-treated mice rapidly decreased and returned to normal levels only 9 days after the treatment, while such leukocytopenia was prevented to some extent and the leukocyte count was restored completely up to 7 days by post-CY-treatment with Lenolate. Furthermore, the treatment with Lenolate augmented the inactivation of virus by PMN. However, the virus inactivation by alveolar macrophages was modified only slightly by Lenolate treatment. In addition, Lenolate-treatment could potentiate antibody-dependent cell-mediated cytotoxicity of PMN against the virusinfected target cells, and the production of serum neutralizing antibody to influenza virus in untreated and CY-treated mice. Lenolate revealed neither antiviral nor interferon inducing-activities. The augmented protection against influenza virus infection in immuno-compromised hosts by Lenolate may be attributed mainly to a partial prevention of a decrease in the number and activity of PMN and a recovery from the depressed values.