Primary antibody response to keyhole limpet hemocyanin in rat as a model for immunotoxicity evaluation

Gore, Elizabeth R.; Gower, Jill; Kurali, Edit; Sui, Jui-Lan; Bynum, Jane; Ennulat, Daniela; Herzyk, Danuta J.

doi:10.1016/j.tox.2003.12.003

Cited by 67 publications

(44 citation statements)

References 17 publications

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“…It was observed that increasing amounts of KLH produced increased responses until a plateau was reached in which 100, 200, and 300 μg per animal produced similar IgM responses (Peachee et al, 2005). Accordingly, we utilized 100 μg/animal as our sensitizing dose consistent with what other researchers were reporting in the peer reviewed literature Gore et al, 2004). However, when we conduced additional studies in rodents with higher sensitizing amounts of KLH, similar to those used in dogs and monkeys (Finco-Kent and Kawabata 2005;Piccotti et al, 2005), even greater levels of antibody production were elicited.…”

Section: Comparison Of the Sensitivity Of The Plaque Assay And Klh Elmentioning

confidence: 94%

“…In addition to the endpoint evaluated, multiple T-dependent antigens are available and utilized in immunotoxico-logical evaluations. Among those most often used include SRBC, keyhole limpet hemocyanin (KLH), chicken gamma globulin and tetanus toxiod (Luster et al, 1988;Temple et al, 1993;Smith et al, 2003;Gore et al, 2004). Even when the same T-dependent antigen, e.g., KLH, is utilized, the amount used to sensitize the rodent for evaluation of the primary antibody response can have marked differences on the results obtained (Peachee et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Primary Immune Responses to SRBC and KLH in Rodents

White

Sheth

Peachee

2007

Journal of Immunotoxicology

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In rodents, the Plaque Assay, T-dependent antibody response to sheep erythrocytes (SRBC), has been reported to be a sensitive and predictive functional immune assay for detecting immunomodulatory compounds. However, various laboratories have chosen to use ELISA-based assays for evaluating the primary immune response in rodents. The ELISA-based assays offer several advantages over the Plaque Assay, which make them attractive for use in immunotoxicological evaluations. Among the most popular antigens used in the ELISA-based assays are SRBC and more recently KLH. While the Plaque Assay and the ELISA-based assays are both capable of evaluating the humoral immune response, they are measuring different endpoints. The Plaque Assay focuses primarily on splenic effects. ELISA-based assays, which use serum from immunized animals, are holistic in nature in that these assays measure effects of antibody production on the spleen, lymph nodes, and bone marrow. Depending on the drug or compound evaluated, different effects and degrees of sensitivity can be seen with the Plaque Assay and ELISA-based assays. One recent finding is that the sensitizing dose of KLH used in the KLH ELISA differentially affects the responses observed in rodents. Even within the same species, different strains of mice and rats produce different magnitudes of responses to the same sensitizing dose. A key component of this discussion focuses on the sensitivity of the Plaque Assay as compared to KLH ELISA-based assays. These assays were evaluated by comparing the response obtained following administration of several known immunosuppressive agents, including cyclophosphamide, azathioprine, cyclosporine A and dexamethasone. The effects on the primary IgM immune response in the B 6 C 3 F 1 mice, the primary immunotoxicological rodents used by National Toxicology Program, and in the Sprague-Dawley rat, the primary rodent models used by industry are addressed.

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Section: Comparison Of the Sensitivity Of The Plaque Assay And Klh Elmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Comparison of Primary Immune Responses to SRBC and KLH in Rodents

White

Sheth

Peachee

2007

Journal of Immunotoxicology

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“…Furthermore, including IgG analysis for the secondary response beyond the primary response may improve the sensitivity of the TDAR. It is important to note that IgG analysis demonstrated greater sensitivity for the detection of immunosuppressive effects by FK506 and cyclosporine than IgM analysis in several rat TDAR studies (Ulrich et al, 2004;Gore et al, 2004;Smith et al, 2003). Indeed, we have demonstrated that the secondary IgG response to KLH was the most sensitive indicator to detect cyclosporineinduced immunosuppression in our rat TDAR model with twice immunizations (Kawai et al, 2010).…”

Section: Discussionmentioning

confidence: 71%

“…Higher primary IgM production induced by intravenous immunization may be related to higher systemic exposure to the KLH resulting in the splenocyte reactions. Similarly, KLH immunization by the intravenous route in rats resulted in a greater anti-KLH IgM production than the subcutaneous or footpad routes (Gore et al, 2004). In addition, no immune-mediated adverse effects were observed in any dog following intravenous injection with KLH unlike sheep erythrocytes which induced an anaphylactic-like response in dogs following intravenous dosing (Haggerty, 2007).…”

Section: Discussionmentioning

confidence: 93%

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Evaluation of canine T-cell dependent antibody response to the primary and secondary immunization with keyhole limpet hemocyanin

et al. 2013

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-T-cell dependent antibody response (TDAR) incorporating both primary and secondary responses to keyhole limpet hemocyanin (KLH) in canine models have not yet been fully understood. To develop a practical dog TDAR model, we characterized primary and secondary antibody responses by intravenous or intramuscular immunization of KLH twice at intervals of 8 days during a 28-day course of study. Primary immunization with KLH by both routes induced a maximum IgM response on 6 to 8 days after the treatment, whereas the IgG response started 6 to 8 days after the treatment with relatively low levels. Remarkable increases in anti-KLH IgG levels (about 10-times compared with the primary response) were produced 5 to 7 days after the secondary KLH immunization by both routes. These results indicate that IgM-predominant and IgG-predominant responses were respectively induced by the primary and secondary immunization. Furthermore, the intravenous route showed higher baseline titers of primary and secondary anti-KLH IgM responses, suggesting that intravenous immunization of KLH might be a more suitable method for immunotoxicity evaluation. No remarkable inter-individual variability was noted in our canine models. Treatment with cyclophosphamide at 2 mg/kg/day for a consecutive 28 days significantly suppressed primary and secondary anti-KLH IgM and IgG responses induced by KLH injection on Days 15 and 23 of CPA treatment. These results demonstrate that these experimental designs could provide valuable information about the influence on both the primary and secondary humoral immune responses in dogs when exposed to potential immunomodulatory drugs.

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Functional Cellular Responses and Cytokine Profiles

Gore

2008

Immunotoxicology Strategies for Pharmaceutical Safety Assessment

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Primary antibody response to keyhole limpet hemocyanin in rat as a model for immunotoxicity evaluation

Cited by 67 publications

References 17 publications

Comparison of Primary Immune Responses to SRBC and KLH in Rodents

Comparison of Primary Immune Responses to SRBC and KLH in Rodents

Evaluation of canine T-cell dependent antibody response to the primary and secondary immunization with keyhole limpet hemocyanin

Functional Cellular Responses and Cytokine Profiles

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