Immunodeficient Dwarfism in Dogs: A Model for Neuroimmunomodulation

Roth, James A.; Goff, B. L.; Monroe, William E.

doi:10.3109/00207458808990705

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…The dog is an important immunological model for mechanism work for diseases such as atopy, rheumatoid arthritis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, autoimmune thyroiditis, autoimmune dermal conditions and systemic lupus erythematosis (Pedersen and Pool, 1980). Imunodeficient dwarfism is a relevant model for elucidating the endocrine role of the thymus in its relationships between the neuroendocrine and immune systems in pre-pubertal dogs (Roth et al, 1988). Moreover, the predictivity of pharmaceutical agent human toxicities by preclinical animal species is almost 50% from dog or primate studies, but very few toxicities are identified from rat studies alone (Olson et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Capture ELISA and flow cytometry methods for toxicologic assessment following immunization and cyclophosphamide challenges in beagles

2000

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The purpose of this subacute 22-day study was to evaluate methods for canine circulating immunoglobulins (IgM, IgG, and IgE) and select B- and T-lymphocyte populations (CD4-helpers, CD8-suppressors, pan-T and pan-B) for immunotoxicity testing using an organ system (concordance) approach. The challenge substance for immunoglobulin testing was repeated immunization with six-way distemper vaccination (DHLAPP), while the challenge substance for leukocyte subpopulations was treatment with cyclophosphamide. Immunoglobulin measurements were made by capture enzyme-linked immunosorbent assay (ELISA), and leukocyte immunophenotyping by fluorescein isothiocyanate/phycoerythrin conjugation (flow cytometry). A battery of parameters that would be used in a typical regulatory study were taken to aid interpretation of the data generated by these methods. Body weights, food consumption, clinical observations, complete clinical chemistry and urinalysis measurements were taken. Gross pathology and micropathology of sternal bone marrow, spleen, mesenteric and retropharyngeal lymph nodes, thymus, liver and kidney were completed. The ELISA method demonstrated acceptable intra-assay reproducibility for IgM, IgG and IgE, with values in good agreement as reported for radial immunodiffusion. The immunologic challenge demonstrated a biological trend of an increase in IgM that preceded an increase in IgG with no discernible trend in IgE response, and no abnormalities in lymphocyte subpopulations. Principle flow cytometry findings related to cyclophosphamide were that the relative percent of B cells decreased dramatically and progressively after compound administration; being statistically decreased in males on day 22 compared with day -5. The relative percent CD4 and CD8 contribution increased, but the CD4/CD8 ratio remained relatively unchanged as total white blood cells decreased progressively. The increase in relative percent CD4 (males only) was statistically significant according to a two-sample t-test on days 17, 20 and 22 when compared with the pre-treatment day -5. There was a relative percent increase in CD5-panT, but absolute numbers were dramatically decreased. We conclude that an organ system approach to assessment of the immune system which incorporates humoral antibody, enumeration of lymphocyte populations and pathologic evaluation of the lymphoreticular organs assists in the interpretation of an adverse toxicological response. The ELISA method for measurement of Igs detected the expected levels of IgG, IgM and IgE due to repeated vaccinations and to cyclophosphamide treatment. The flow cytometry method was acceptable for measuring select canine lymphocyte populations and detecting the expected decrease in B cells due to cyclophosphamide treatment. Both methods may be added to a testing battery for assessing immunotoxicityl in canine regulatory studies.

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Section: Introductionmentioning

confidence: 99%

Capture ELISA and flow cytometry methods for toxicologic assessment following immunization and cyclophosphamide challenges in beagles

2000

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Possible Association of Thymus Dysfunction with Fading Syndromes in Puppies and Kittens

Roth

1987

Veterinary Clinics of North America: Small Animal Practice

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Wasting" or "fading" syndromes are common causes of death in both puppies and kittens. These poorly defined syndromes are generally characterized by anorexia, lethargy, and emaciation during the first few weeks of life and often lead to death with no apparent cause. The terms "wasting" and "fading" describe this general syndrome and will be used interchangeably throughout this article. The fading syndrome can cause major problems in breeding colonies, especially if inbreeding has occurred. 11 Many possible causes have been suggested, including viral infections, bacterial septicemias, nutritional inadequacies, toxins, and environmental factors. 6 • 7 • 11 • 27 • 28 • 31 ·33. 4 0-4 2 • 44 Several of these factors are probably capable of causing neonatal wasting and death and should be considered in a differential diagnosis. Infectious canine hepatitis virus and beta-hemolyt!c streptococcus infection in puppies 7 • 28 • 44 and feline infectious peritonitis infection in kittens 6 • 27 · 31 • 33 • 40 · 41 have been strongly implicated as causes of fading and death iii some cases. However, several authors have reported that infectious agents could not be isolated from a large proportion of puppies and kittens that fade and die, and that lesions severe enough to cause death could not be.found. 6 • 7 • 11 • 20 • 33 • 42 Therefore, the cause of the fading syndrome remains a mystery in most cases. The status of the thymus gland has not received adequate attention in diagnosis and therapy of wasting syndromes of puppies and kittens. In some species, neonatal thymectomy results in a fatal wasting syndrome 17 • 29 that can be prevented by soluble factors from the thymus. 25 • 32 This article will focus on the role of the thymus gland in maintaining the health of young animals and on how thymus dysfunction may contribute to some cases of wasting and death. Current knowledge about thymus hormones will be reviewed bfiefly, and

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Immunodeficient Dwarfism in Dogs: A Model for Neuroimmunomodulation

Cited by 2 publications

References 10 publications

Capture ELISA and flow cytometry methods for toxicologic assessment following immunization and cyclophosphamide challenges in beagles

Capture ELISA and flow cytometry methods for toxicologic assessment following immunization and cyclophosphamide challenges in beagles

Possible Association of Thymus Dysfunction with Fading Syndromes in Puppies and Kittens

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