Effective immune clearance of influenza virus requires an immune system that is intact and functioning normally. Host resistance models have therefore been used to evaluate the effect of an antiviral treatment on virus clearance, as an indicator of the immunocompetence of an animal during or after treatment and to test for the immunotoxicity of a particular agent (Burleson and Burleson, 2007). Mechanistic studies to detect immunotoxicity should include measuring innate, humoral and cell mediated immune responses, through parameters such as cytokine and interferon production, macrophage function, and natural killer cell function and cytotoxic T lymphocyte activity, as well as influenza-specific antibody during or after drug treatment. For example, the compound 3M-011, a synthetic human TLR7/8 agonist, was evaluated for antiviral efficacy and immunotoxicity in a rat HR model, which parallel human influenza infection, both with respect to time course and development of respiratory tract lesions (Hammerbeck et al., 2007, Burleson and Burleson, 2007). Intranasal (IN) administration of 3M-011 significantly inhibited H3N2 influenza viral replication in the nasal cavity when animals were pretreated or therapeutically treated with the compound. Inhibition correlated closely with induction of type I interferon and to a lesser extent with other cytokines such as TNF-α, IL-12, and IFN-γ from rat peripheral blood mononuclear cells, and seemed to have no negative effect on the immune response to infection.