Endogenous Glucocorticoids Play a Positive Regulatory Role in the Anti-Keyhole Limpet Hemocyanin In Vivo Antibody Response

Abstract

Glucocorticoids (GCs) are commonly reported to be immunosuppressive. Studies that support this involve the administration of synthetic GCs such as dexamethasone at high pharmacological doses and using in vitro assay systems that may have limited relevance to the role of GCs during normal in vivo immune responses. Therefore, the following experiments tested the conclusion that GCs are generally immunosuppressive. Adult male Sprague Dawley rats received adrenalectomy (ADX) or sham surgery. ADX rats were given either basal corticosterone (CORT) replacement in their drinking water (25 μg/ml) or no CORT. Rats were immunized with keyhole limpet hemocyanin (KLH), and blood samples were taken. ADX rats with no CORT replacement had reduced anti-KLH IgM and IgG responses compared with sham-operated controls. ADX rats that received basal CORT replacement had partially restored anti-KLH IgM, but still had suppressed anti-KLH IgG. Administration of GC receptor type I (RU28318) and type II (RU40555) receptor antagonists also reduced the anti-KLH IgM and IgG responses. ADX rats that received both basal CORT replacement and low dose injections of CORT on days 5 and 7 after KLH had anti-KLH IgG levels equal to those of sham-operated controls. Finally, the GC elevation 4–7 days after immunization may play a role in stimulating the IgM to IgG2a switch. GC receptor blockade reduced the anti-KLH IgG2a and splenic IFN-γ, but not the anti-KLH IgG1, response. Given that IFN-γ is an important regulator of the IgM to IgG2a switch, it is possible that the small rise in GC found 4–7 days after KLH facilitates IgG2a isotype switching.

Exposure to acute physical and psychological stress alters the response of rat macrophages to corticosterone, neuropeptide Y and beta-endorphin

“…Our findings that high concentrations of CORT diminished macrophage adherence while a low concentration increased H 2 O 2 release together support the general view that the physiological role of endogenous glucocorticoids is to maintain and optimise the immune response (Fleshner et al 2001), since low concentrations of CORT produce immunoenhancement while higher concentrations are immunosuppressive (Dhabhar and McEwen 1999). However, CORT diminished zymosan engulfment at all concentrations tested.…”

Immunological substance testing on human lymphatic micro-organoids in vitro

“…The immune suppressive drug dexamethasone reduces cytokine secretion within this in vitro model completely, especially proinflammatory and TH1 cytokines (Torres et al, 2005), but enhances the production of IgM antibodies as described for in vivo (Fleshner et al, 2001) as well as for in vitro (Sakuma et al, 2001). Therefore this HuALN model physically reflects the immunological effects of vaccines and virus preparations and immune-modulating substances.…”

Upregulations of Glucocorticoid-Induced Leucine Zipper by Hypoxia and Glucocorticoid Inhibit Proinflammatory Cytokines under Hypoxic Conditions in Macrophages

“…injection with 3% pentobarbital sodium (1 ml·kg 21 body weight), and adrenal glands were removed by the dorsal approach as described by Fleshner et al (37). Sham animals underwent the same surgery, except the adrenal glands were left intact (37). Adrenalectomized (ADX) rats were given 0.9% saline ad libitum to compensate for sodium loss after the operation and allowed to recover for 1 wk before Dex supplement and/or hypoxia exposure.…”

“…injection with 3% pentobarbital sodium (1 ml·kg 21 body weight), and adrenal glands were removed by the dorsal approach as described by Fleshner et al (37). Sham animals underwent the same surgery, except the adrenal glands were left intact (37).…”