TY - JOUR
T1 - Apomorphine-susceptible and apomorphine-unsusceptible Wistar rats differ in their susceptibility to inflammatory and infectious diseases
T2 - A study on rats with group-specific differences in structure and reactivity of hypothalamic-pituitary-adrenal axis
AU - Kavelaars, Annemieke
AU - Heijnen, Cobi J.
AU - Ellenbroek, Bart
AU - Van Loveren, Henk
AU - Cools, Alexander
PY - 1997
Y1 - 1997
N2 - Variability in susceptibility to diseases is a well known phenomenon that has been attributed to genetic and environmental factors. At the level of the immune system, the reactivity of two types of T helper cells (Th1 and Th2 cells) plays an important role in determining disease susceptibility. Inflammatory (autoimmune) diseases are stimulated by cytokines produced by Th1 cells. Th2 cytokines stimulate antibody production (e.g., IgE) and eosinophilia as observed in allergic reactions or during parasitic infections. We describe here that the reactivity in a Th1 or a Th2 disease model significantly differs between individual rats that show group-specific differences in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis, as well as in their behavioral responses to stress. We used two outbred lines of Wistar rats, apomorphine-susceptible rats that have a relatively hyperreactive HPA axis (APO-SUS) and apomorphine-unsusceptible rats that have a relatively hyporeactive HPA axis (APO-UNSUS). APO-SUS, but not APO-UNSUS, rats generated a vigorous Th2-dependent IgE response after infection with the nematode Trichinella spiralis. In contrast, APO-UNSUS, but not APO-SUS, rats were susceptible for Th1-mediated experimental autoimmune encephalomyelitis. Investigation of cytokine responses of splenocytes revealed that the ratio of mRNA expression for Th1-derived interferon (IFN)-γ and mRNA expression of Th2-derived interleukin-4 (IL-4) was significantly smaller in APO-SUS than in APO-UNSUS rats. In conclusion, individual differences in structure and reactivity of the neuroendocrine system co-occur with group-specific differences in susceptibility to inflammatory and infectious diseases.
AB - Variability in susceptibility to diseases is a well known phenomenon that has been attributed to genetic and environmental factors. At the level of the immune system, the reactivity of two types of T helper cells (Th1 and Th2 cells) plays an important role in determining disease susceptibility. Inflammatory (autoimmune) diseases are stimulated by cytokines produced by Th1 cells. Th2 cytokines stimulate antibody production (e.g., IgE) and eosinophilia as observed in allergic reactions or during parasitic infections. We describe here that the reactivity in a Th1 or a Th2 disease model significantly differs between individual rats that show group-specific differences in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis, as well as in their behavioral responses to stress. We used two outbred lines of Wistar rats, apomorphine-susceptible rats that have a relatively hyperreactive HPA axis (APO-SUS) and apomorphine-unsusceptible rats that have a relatively hyporeactive HPA axis (APO-UNSUS). APO-SUS, but not APO-UNSUS, rats generated a vigorous Th2-dependent IgE response after infection with the nematode Trichinella spiralis. In contrast, APO-UNSUS, but not APO-SUS, rats were susceptible for Th1-mediated experimental autoimmune encephalomyelitis. Investigation of cytokine responses of splenocytes revealed that the ratio of mRNA expression for Th1-derived interferon (IFN)-γ and mRNA expression of Th2-derived interleukin-4 (IL-4) was significantly smaller in APO-SUS than in APO-UNSUS rats. In conclusion, individual differences in structure and reactivity of the neuroendocrine system co-occur with group-specific differences in susceptibility to inflammatory and infectious diseases.
KW - T cells
KW - Trichinella spiralis
KW - experimental autoimmune encephalomyelitis
KW - hypothalamus- pituitary-adrenal axis
KW - interferon-γ
KW - interleukin-4
KW - rats
UR - http://www.scopus.com/inward/record.url?scp=0030988615&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030988615&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.17-07-02580.1997
DO - 10.1523/jneurosci.17-07-02580.1997
M3 - Article
C2 - 9065517
AN - SCOPUS:0030988615
SN - 0270-6474
VL - 17
SP - 2580
EP - 2584
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 7
ER -