title: Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats.
abstract: Prenatal alcohol exposure (PAE) has adverse effects on the development of numerous physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system. HPA hyper-responsiveness and impairments in immune competence have been demonstrated. The present study investigated immune function in PAE females utilizing an adjuvant-induced arthritis (AA) model, widely used as a model of human rheumatoid arthritis. Given the effects of PAE on HPA and immune function, and the known interaction between HPA and immune systems in arthritis, we hypothesized that PAE females would have heightened autoimmune responses, resulting in increased severity of arthritis, compared to controls, and that altered HPA activity might play a role in the immune system changes observed. The data demonstrate, for the first time, an adverse effect of PAE on the course and severity of AA in adulthood, indicating an important long-term alteration in functional immune status. Although overall, across prenatal treatments, adjuvant-injected animals gained less weight, and exhibited decreased thymus and increased adrenal weights, and increased basal levels of corticosterone and adrenocorticotropin, PAE females had a more prolonged course of disease and greater severity of inflammation compared to controls. In addition, PAE females exhibited blunted lymphocyte proliferative responses to concanavalin A and a greater increase in basal ACTH levels compared to controls during the induction phase, before any clinical signs of disease were apparent. These data suggest that prenatal alcohol exposure has both direct and indirect effects on inflammatory processes, altering both immune and HPA function, and likely, the normal interactions between these systems.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Xingqi
authors.initials: X
authors.lastname: Zhang
authors.forename: Ni
authors.initials: N
authors.lastname: Lan
authors.forename: Paxton
authors.initials: P
authors.lastname: Bach
authors.forename: David
authors.initials: D
authors.lastname: Nordstokke
authors.forename: Wayne
authors.initials: W
authors.lastname: Yu
authors.forename: Linda
authors.initials: L
authors.lastname: Ellis
authors.forename: Gary G
authors.initials: GG
authors.lastname: Meadows
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007107:Immune System / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone