Effect of Mycoplasma fermentans on brain PGE(2): role of glucocorticoids and their receptors.
OBJECTIVE
Mycoplasmas are a group of eubacteria, which cause various diseases in animals and in humans, and can contribute to diseases produced by other infectious agents, particularly HIV. We have recently reported that intracerebral administration of Mycoplasma fermentans (MF) produces both neuroendocrine and behavioral alterations. Some of these responses were mediated by MF-induced production of prostaglandin E(2 )(PGE(2)). The aim of this study was to examine the role of glucocorticoids (GC) in regulating MF-induced brain prostaglandin production.


METHODS
Male rats were injected intracerebroventricularly with various doses of heat-inactivated MF, LPS or IL-1 beta and the following parameters were measured: (1) ex vivo production of hippocampal PGE(2), (2) serum levels of ACTH and corticosterone, and (3) binding capacity of [(3)H]-dexamethasone (DEX) to hippocampal cytosol.


RESULTS
MF caused a small increase in hippocampal PGE(2) production, but higher doses failed to produce a further increase. In contrast, the effects of LPS or IL-1 beta on PGE(2) were dose-dependent. Removal of circulating GC by bilateral adrenalectomy significantly enhanced MF-induced brain PGE(2) production. The three immune stimulators increased serum levels of ACTH and corticosterone to the same extent. Finally, MF, but not IL-1 beta increased the specific binding of [(3)H]-DEX to hippocampal cytosol.


CONCLUSIONS
Brain PGE(2) induced by MF is regulated by endogenous GC. These hormones have an attenuating effect on PGE(2 )production, probably through an MF-induced increase in GC binding by brain tissue. This mechanism may be important in the pathological effect of MF within the brain of AIDS patients.
Wohlman
A
A
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Yirmiya
R
R
Gallily
R
R
Weidenfeld
J
J
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000276:immunology; D001667:Binding, Competitive / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D003345:Corticosterone / Q000097:blood; D015232:Dinoprostone / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000097:blood / Q000276:immunology*; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009175:Mycoplasma Infections / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D016858:Mycoplasma fermentans / Q000276:immunology* / Q000472:pathogenicity; D015213:Neuroimmunomodulation / Q000502:physiology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000276:immunology* / Q000378:metabolism
D001426:Bacterial Proteins; D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D003345:Corticosterone