A genetic model of stress displays decreased lymphocytes and impaired antibody responses without altered susceptibility to Streptococcus pneumoniae

Stress pathways affect immune function, the most notable of these pathways being activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although HPA activation has generally been relegated to an immunosuppressive role, recent evidence suggests that stress and HPA activation can be immunoenhanc ing in certain situations. To investigate specific effects of stress on imm une function, we used a genetic model of chronic stress wherein transgenic mice overexpress corticotropin-releasing hormone (CRH), a primary mediator of the stress response. In these mice, CRH is overproduced in the brain, le ading to chronic activation of the HPA axis. We found that CRH-transgenic m ice have decreased leukocyte numbers in lymphoid compartments, with prefere ntial loss of B lymphocytes. They also exhibit decreased Ab production and impaired isotype switching in response to immunization with a thymus-depend ent Ag, phosphocholine-keyhole limpet hemocyanin. Despite these deficits, i mmunization protected CRH-transgenic and wild-type mice equally well agains t lethal challenge with Streptococcus pneumoniae, an encapsulated Gram-posi tive bacterium known to require Ab-mediated opsonization for clearance. Whi le IgG responses are severely depressed in these mice, IgM titers are only modestly decreased. This fairly robust IgM response may be sufficient to pr otect against S. pneumoniae. Additionally, while total leukocyte numbers ar e decreased in these mice, neutrophil numbers are increased. This increase in number of neutrophils may compensate for the depressed IgG response, all owing adequate host defense during chronic stress.