Systemic blockade of complement C5a receptors reduces lipopolysacharride-induced responses in the paraventricular nucleus and the central amygdala.
The complement anaphylatoxin C5a is a potent mediator of the innate immune response to infection. Recent evidence also reveals that C5a contributes to central nervous system effects in addition to its well-known peripheral functions. However, it is not known if C5a has a role in the activation of the hypothalamic-pituitary-adrenal (HPA) axis; a critical cascade that exemplifies neuroimmune interactions between the periphery and the brain. In the present study we examined if systemic pre-treatment with a C5a receptor antagonist, PMX53, can affect lipopolysaccharide-induced (LPS; 1 mg/kg, i.p.) activation of the HPA axis in the rat. Using Fos protein as a marker of neuronal activation, we found that systemic administration of PMX53 reduced the LPS-induced activation of paraventricular corticotropin-releasing factor (PVN CRF) and central amygdala cells. However, PMX53 did not alter LPS-induced responses in the bed nucleus of the stria terminalis, nucleus tractus solitarius and ventrolateral medulla. Our findings demonstrate that C5a may have a role in the activation of the HPA axis in response to systemic LPS.
Crane
James W
JW
Queensland Brain Institute, University of Queensland, St. Lucia, Queensland 4072, Australia.
Buller
Kathryn M
KM
D000679:Amygdala / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D015936:Complement C5a / Q000276:immunology*; D003346:Corticotropin-Releasing Hormone / Q000276:immunology / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology*; D018836:Inflammation Mediators; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D015213:Neuroimmunomodulation / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors / Q000276:immunology*
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a; D003346:Corticotropin-Releasing Hormone