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Lymphocyte proliferative response in brown bears: cytokine role and glucocorticoid effect
M Musiani1, L Gentile, M Valentini
1Istituto di Patologia Umana e Medicina Sociale, Università G. D'Annunzio, Chieti, Italy. mc5798@mclink.it
Insights
Brown bear lymphocytes show a robust proliferative response to mitogens, greater than humans. Interleukin 1 and 2 enhance this response, while dexamethasone inhibits it, offering insights for bear immunology and potential therapeutic applications.
Area of Science:
- Immunology
- Comparative immunology
- Veterinary immunology
Background:
- Lymphocyte stimulation and proliferation are crucial for immune responses against various antigens.
- Understanding bear immune cell function is vital for wildlife conservation and health management.
Purpose of the Study:
- To investigate the in vitro proliferative capacity of brown bear lymphocytes.
- To compare bear lymphocyte responses to human responses.
- To assess the effects of specific cytokines and a corticosteroid on bear lymphocyte proliferation.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) were isolated from brown bears (Ursus arctos) using Ficoll-Hypaque density gradient centrifugation.
- PBMC and peripheral blood lymphocytes (PBL) were stimulated with mitogens (phytohemagglutinin, Concanavalin A) and cultured with recombinant human cytokines (IL1, IL2, TGF-beta) or dexamethasone (DEX).
- Lymphocyte proliferation was measured and compared between bears, humans, and mice.
Main Results:
- Bear PBMC exhibited a significantly greater proliferative response to PHA and ConA compared to human PBMC.
- Transforming growth factor beta (TGF-beta) inhibited bear PBMC proliferation similarly to humans.
- Interleukin 1 (IL1) and Interleukin 2 (IL2) significantly augmented lymphocyte proliferation, while dexamethasone (DEX) showed a lesser inhibitory effect on bear PBMC compared to humans and mice. IL2 addition reduced DEX inhibition in bears and humans.
Conclusions:
- Brown bear lymphocytes possess a strong proliferative capacity, exceeding that of humans in response to certain mitogens.
- The modulatory effects of IL1, IL2, and DEX on bear lymphocyte proliferation suggest potential applications in enhancing immune responses, such as in vaccinations.
- Dexamethasone's differential inhibitory effect highlights its potential to impact bear immune-mediated diseases.
Abstract:
Lymphocyte stimulation and proliferation play a pivotal role in the immune response to soluble as well as to cellular, bacterial, and viral antigens. In this study, peripheral blood mononuclear cells (PBMC), mainly composed of lymphocytes, were separated by Ficoll-Hypaque density gradient centrifugation from 50-ml jugular vein blood samples drawn from six captive and five wild-caught brown bears (Ursus arctos) (eight Apennine brown bears from the Italian population; three of undetermined origin). Stimulation of cultured bear PBMC with the two classical T lymphocyte mitogens phytohemagglutinin (PHA) and Concanavalin A (ConA) was followed by a significantly greater proliferative response than that shown by human PBMC (n = 11) (PHA: T = 4.03, d.f. = 20, P = 0.001; ConA: T = 4.25, d.f. = 20, P < 0.0005; Student's t-test, oneway ANOVA). As in humans, the PBMC proliferative response in bears was markedly (> 50%) inhibited by addition of transforming growth factor beta (TGF beta) human recombinant cytokine to the culture. Further fractionation provided a cell preparation extremely rich in peripheral blood lymphocytes (PBL) (mean +/- SD = 96.1 +/- 1.7%). Addition of interleukin 1 (IL1) or interleukin 2 (IL2) human recombinant cytokines to cultured PBL stimulated with a suboptimal concentration of mitogens resulted in a ninefold increase in the lymphocyte proliferative response. Dexamethasone (DEX, a synthetic analog of hydrocortisone) inhibited the bear PBMC proliferative response by 22.2 +/- 4.3% (mean +/- SD), compared with 46.2 +/- 6.9% and 91.8 +/- 8.1% (mean +/- SD) in humans and mice (n = 11) (Mus domesticus), respectively. Inhibition of the brown bear and human PBMC responses was markedly (> 60%) reduced by the addition of IL2. The finding that IL1 and IL2 augment and that DEX inhibits bear lymphocyte proliferative response suggests that these cytokines can be used to increase the immune response in vaccinations, and that DEX may hamper several immunologically mediated diseases.