The role of endogenous steroid hormones in the generation of T helper 2-mediated autoimmunity in mercuric chloride-treated Brown-Norway rats.
Injection of Brown-Norway rats with mercuric chloride (HgCl2) activates a T helper type 2 (Th2) autoimmune response, with production of a number of autoantibodies and vasculitis primarily affecting the gut. Glucocorticoids have been shown to suppress Th1 and to promote the development of Th2-type responses. Conversely dehydroepiandrosterone (DHEA) promotes Th1 responses with suppression of Th2 responses. This study set out to define the role of these hormones in this animal model. Rats were adrenalectomized (Adx) with no steroid replacement (n = 11), Adx with basal steroid replacement given by a 25 mg corticosterone pellet inserted subcutaneously (n = 13), or sham-Adx (n = 14) prior to administration of HgCl2. In both groups of Adx animals there was a delay in the production of immunoglobulin E (IgE) and serum concentrations on day 9 were marginally lower (P = 0.035, repeated measures ANOVA). All of the animals Adx with no steroid replacement and two Adx animals with steroid replacement died between 10 and 14 days after HgCl2 challenge. There was no difference in the severity of caecal vasculitis between the groups. A significant increase in adrenal size was noted following administration of HgCl2. Administration of subcutaneous DHEA implants (100 mg and 200 mg) had no significant effect on IgE concentrations or severity of vasculitis. These observations do not support the hypothesis that corticosterone and DHEA play a central role in setting the Th1/Th2 balance in this experimental Th2-mediated autoimmune disease; in contrast with the Th1-mediated autoimmune disease experimental allergic encephalomyelitis where corticosterone plays a key role in immunoregulation.
MacPhee
I A
IA
Departments of *Renal Medicine and Pathology, St. George's Hospital Medical School, Cranmer Terrace, London, UK.
Turner
D R
DR
Oliveira
D B
DB
D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D015551:Autoimmunity; D002429:Cecal Diseases / Q000139:chemically induced / Q000276:immunology; D003345:Corticosterone / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology*; D006984:Hypertrophy; D007073:Immunoglobulin E / Q000097:blood*; D008627:Mercuric Chloride; D051381:Rats; D011914:Rats, Inbred BN; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D014657:Vasculitis / Q000139:chemically induced / Q000276:immunology
D005938:Glucocorticoids; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D019314:Dehydroepiandrosterone Sulfate; D003345:Corticosterone