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Host-resistance assays

With the exception of whole-animal host resistance assays, the actual testing approach can be described as ex vivo-in vitro in that exposure of the immune system to potential immunotoxicants takes place in vivo, with subsequent immunological evaluation taking place in vitro. Although this approach obviates many uncertainties (effect of xenobiotics on primary or secondary lymphoid tissue, potential requirements for metabolism/bio-transformation, etc.), the use of whole animals presents many secondary issues, such... [Pg.74]

Host-resistance assays can be used to assess the overall immunocompetence of the humoral or cell-mediated immune systems of the test animal (host) to fend off infection with pathogenic microbes, or to resist tumorigenesis and metastasis. These assays are performed entirely in vivo and are dependent on all of the various components of the immune system to be functioning properly. Thus, these assays may be considered to be more biologically relevant than in vitro tests that only assess the function of cells from one source and of one type. Since these assays require that the animal be inoculated with a pathogen or exogenous tumor cell, they cannot be performed as part of a general preclinical toxicity assessment, and are thus classified as Type 2 tests in the revised Redbook. These assays are also included as Tier II tests by the NTP. [Pg.570]

Host-resistance assays offer a way to determine the relative significance of a compound-related decrease in immune function, commonly one of such... [Pg.423]

Wierda D. Can host resistance assays be used to evaluate the immunotoxicity of pharmaceuticals Hum Exp Toxicol 2000 19 244-5. [Pg.473]

TABLE 5.1-1 Commonly Used Host Resistance Assays... [Pg.164]

MODELS OF HOST RESISTANCE TO INFECTIONS Influenza Host Resistance Assay... [Pg.165]

The algorithm in Table 5.1-2 provides a path to ensure a thorough immuno-toxicological safety evaluation for therapeutics. The influenza host resistance assay is a well-characterized model and can serve as a biomarker for evaluating the overall health of the immune system. Therapeutic agents can be evalu-... [Pg.165]

TABLE 5.1-2 Algorithm for Immunotoxicity Evaluation Using Host Resistance Assays Generalized Assay to Evaluate the Overall Health of the Immune System... [Pg.165]

B) Mechanistic immune function assays associated with influenza host resistance assay that may or may not be included ... [Pg.165]

The influenza virus host resistance model has been characterized in mice and rats, and has been widely used to evaluate the potential immunotoxicity of therapeutics. Influenza virus is used as the infectious challenge agent and administered intranasally in a 28-day repeat-dose study. Mice or rats are dosed for 7 days, infected and then dosed for an additional 21 days. Viral clearance is quantified by measuring infectious virus (plaque-forming units) at various times following infection. Dexamethasone may be used as a positive immunomodulatory control. This host resistance assay has been used in Balb/c, C57BL/6, and B6C3F1 mice and Fischer 344 (CDF), Brown Norway, and... [Pg.166]

The therapeutic agent should be further tested in the murine cytomegalovirus (MCMV) latent virus reactivation model if results from the influenza host resistance assay indicate a decreased functional activity for either NK, CTL, or TDAR, or a decrease in CD4+ cells as observed by immunopheno-typing. The MCMV latent virus reactivation model is discussed in detail below. The test article should be tested in the Streptococcus pneumoniae systemic model for encapsulated bacteria if immunophenotyping or histopathology, done in conjunction with the influenza host resistance model, reveals a decrease in the number of marginal zone B (MZB) cells. MZB cells are critical in host defense against bloodborne encapsulated bacteria and this host resistance assay is discussed in detail below. [Pg.167]

The algorithm in Table 5.1-3 lists targeted host resistance assays that are useful to evaluate specific immunotoxicity questions. [Pg.167]

Anti-Inflammatory Therapeutics. The Streptococcus pneumoniae pulmonary host resistance assay is recommended for anti-inflammatory therapeutics (Komocsar et al., 2007). The Streptococcus pneumoniae pulmonary host resistance model in Lewis rats was used to assess the effects of anti-inflammatory agents on innate immunity. The model was able to predict potential drug suppression of the innate immune response to Streptococcus pneumoniae. The authors stated the ability to rank order the severity of innate immune suppression with multiple test articles in the same study made this model effective in screening potential drug candidates. [Pg.168]

The influenza host resistance assay is able to evaluate the overall health of the immune system, as well as to evaluate mechanistic immunological function of... [Pg.172]

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See also in sourсe #XX -- [ Pg.41 , Pg.42 , Pg.70 ]



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