Apomorphine-susceptible and apomorphine-unsusceptible Wistar rats differ in their susceptibility to inflammatory and infectious diseases: a study on rats with group-specific differences in structure and reactivity of hypothalamic-pituitary-adrenal axis.
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)-gamma 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.
Kavelaars
A
A
Department of Immunology, University Hospital for Children and Youth "Het Wilhelmina Kinderziekenhuis," 3501 CA Utrecht, The Netherlands.
Heijnen
C J
CJ
Ellenbroek
B
B
van Loveren
H
H
Cools
A
A
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003141:Communicable Diseases / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar / Q000235:genetics*; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma; D001058:Apomorphine