Endogenous glucocorticoids play a positive regulatory role in the anti-keyhole limpet hemocyanin in vivo antibody response.
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 microg/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-gamma, but not the anti-KLH IgG1, response. Given that IFN-gamma 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.
Fleshner
M
M
Department of Kinesiology and Applied Physiology, University of Colorado, Boulder, CO 80309, USA. fleshner@spot.colorado.edu
Deak
T
T
Nguyen
K T
KT
Watkins
L R
LR
Maier
S F
SF
D000284:Administration, Oral; D000315:Adrenalectomy; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D003907:Dexamethasone / Q000008:administration & dosage; D004338:Drug Combinations; D006433:Hemocyanins / Q000008:administration & dosage* / Q000276:immunology; D006727:Hormone Antagonists / Q000008:administration & dosage; D006984:Hypertrophy; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000097:blood; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D000941:Antigens; D004338:Drug Combinations; D006727:Hormone Antagonists; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D011965:Receptors, Glucocorticoid; C075646:RU 40555; D013148:Spironolactone; D015735:Mifepristone; C041006:RU 28318; D003907:Dexamethasone; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D003345:Corticosterone