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Reduced Primary Antibody Responses in a Genetic Animal Model of Depression

From the Psychology Department (E.M.F., K.A.B.), Williams College, Williamstown, MA; Skipper Bowles Center for Alcohol Studies and Department of Psychiatry (D.H.O.), University of North Carolina at Chapel Hill, Chapel Hill, NC; and Division of Molecular Medicine (D.A.L.), Wadsworth Laboratories, New York State Department of Health, Albany, NY.

Address reprint requests to: Elliot Friedman, PhD, Psychology Department, Bronfman Science Center, Williams College, Williamstown, MA 01267. Email: Elliot.M.Friedman{at}williams.edu

OBJECTIVE: Clinical depression is associated with multiple abnormalities of immune function, including reduced virus-specific responses. This study tested the hypothesis that the Flinders Sensitive Line (FSL) rat, a promising genetic animal model of depression, would exhibit reductions in antigen-specific primary antibody responses to immunization.

METHODS: FSL (N = 13) and control Flinders Resistant Line (FRL; N = 14) rats were immunized with the protein antigen keyhole limpet hemocyanin (KLH; 300 µg/kg), and KLH-specific immunoglobulin (Ig)M, IgG, IgG1, and IgG2a responses were measured before and 3, 5, 7, 11, and 14 days after immunization. In separate experiments, production of interferon- (IFN-) by cells from naive and KLH-immunized animals was measured in vitro to determine whether strain differences in antibody production might be associated with differential production of this regulatory cytokine.

RESULTS: KLH-specific production of IgM (p < .01) and IgG2a (p < .05) was significantly reduced in the FSL rats compared with the FRL controls. There were no strain differences in IgG or IgG1 production. Although IFN- production between the two strains was similar in naive animals, cells from KLH-immunized FSL rats produced significantly less IFN- when stimulated with KLH in vitro than cells from KLH-immunized FRL controls (p = .01).

CONCLUSIONS: This study extends previous reports of altered immune function in the FSL rats to include reduced in vivo antigen-specific antibody responses. Moreover, diminished production of IFN- by KLH-primed lymphocytes may contribute to lower antibody production in these animals. Collectively, these data suggest deficiencies in type 1 T-helper cell-mediated immunity in the FSL rats.

Key Words: depression, • Flinders, • antibody, • keyhole limpet hemocyanin, • interferon-.

Abbreviations: BSA = bovine serum albumin;; ELISA = enzyme-linked immunosorbent assay;; FSL = Flinders Sensitive Line;; FRL = Flinders Resistant Line;; IFN- = interferon-;; Ig = immunoglobulin;; IL-2 = interleukin-2;; IP = intraperitoneal;; KLH = keyhole limpet hemocyanin;; MNC = mononuclear cell;; NK = natural killer (cell);; PBS = phosphate-buffered saline;; SEB = staphylococcal enterotoxin B;; Th1 = T-helper cell, type 1.

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