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Departments of
*
Kinesiology and Applied Physiology and
Psychology, University of Colorado, Boulder, CO 80309
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-
, but not the anti-KLH IgG1, response.
Given that IFN- 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.
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