Table I.

Experimental conditions where GCs have been found to increase inflammation

PERIPHERAL
GC dose	GC treatment time	Peripheral Location	Pro-inflammatory effect	Inflammatory stimulus	Reference
Acute stressor	Concurrent	Human PBMCs ex vivo, THP-1 cell line	NFkB activity	None	(Bierhaus et al. 2003)
Basal cort levels	Concurrent	Mouse macrophage cell line	MIF secretion	None	(Calandra et al. 1995)
Dexamethasone	Concurrent	Human PBMCs ex vivo	Cytokines, complement, chemokines	None	(Galon et al. 2002)
Dexamethasone	Concurrent	Human PBMCs ex vivo, THP-1 cell line	5-lipoxygenase	None	(Riddick et al. 1997)
Dexamethasone	Concurrent	THP-1 cell line	IL-1 beta	PMA	(Wang et al. 1997)
Dexamethasone	Concurrent	THP-1 cell line	NFkB activity	PMA	(Wang et al. 1997)
Dexamethasone or prednisolone	>16 hours prior	Human lymphocyte cultures	Proliferation	Mitogens, x- linking Abs, or PMA+ionomycin	(Almawi et al. 1999)
Low stress cort levels	Acute 2hrs prior	Rat leukocytes in vivo	Leukocyte migration	DTH	(Dhabhar et al. 1996)
Low stress cort levels	Concurrent	Rat lymphocyte cultures	Proliferation	IL-2	(Wiegers et al. 1995)
Low stress cort levels	>6 hours prior	Mouse macrophage cell line	NFkB activity	LPS and IFNγ	(Smyth et al. 2004)
Low stress cort levels	>6 hours prior	Mouse macrophage cell line	TNF-alpha, IL-6, nitrite	LPS and IFNγ	(Smyth et al. 2004)
Low stress cort levels	>12 hours prior	Human plasma	TNF-alpha, IL-6	LPS	(Barber et al. 1993)
CENTRAL
GC treatment	GC treatment time	Central Location	Pro-inflammatory effect	Inflammatory stimulus	Reference
Acute stressor	Concurrent	Rat cortex	NFkB activity	None	(Madrigal et al. 2001)
Acute stressor	24 hours prior	Rat brain	IL-1 beta	Peripheral LPS	(Johnson et al. 2002)
Acute stressor	24 hours prior	Rat hippocampal microglia	IL-1 beta	Peripheral LPS	(Frank et al. 2006)
CUS	Chronic 9 days after	Rat prefrontal cortex	Microglia activation	Central LPS	(de Pablos et al. 2006)
CUS	Chronic 9 days after	Rat prefrontal cortex	TNF-alpha	Central LPS	(de Pablos et al. 2006)
CUS	Chronic 9 days after	Rat prefrontal cortex	MAPK signaling	Central LPS	(de Pablos et al. 2006)
CUS	Chronic 14 days prior	Rat hippocampus, frontal cortex	TNF-alpha, IL-1 beta	Peripheral LPS	(Munhoz et al. 2006)
CUS	Chronic 14 days prior	Rat hippocampus, frontal cortex	NFkB activity	Peripheral LPS	(Munhoz et al. 2006)
Dexamethasone	Concurrent	Mouse neuronal cell line	PGD2 synthase	None	(Garcia-Fernandez et al. 2000)
Dexamethasone*	One hour prior	Mouse hippocampus	TNF-alpha, TNF-beta, IL-1 beta	TMT	(Bruccoleri et al. 1999)
High stress cort levels	Chronic 3 days prior	Rat hippocampus	Leukocyte migration	Kainic acid	(Dinkel et al. 2003)
High stress cort levels	Chronic 3 days prior	Rat hippocampus	Microglia activation	Kainic acid	(Dinkel et al. 2003)
High stress cort levels	Chronic 24 hours prior	Rat hippocampal cultures	TNF-alpha, IL-1 beta	Kainic acid	(MacPherson et al. 2005)
Intermediate stress cort levels	Chronic 3 days prior	Rat hippocampus, frontal cortex	TNF-alpha, IL-1 beta	Peripheral LPS	(Munhoz in prep)
Intermediate stress cort levels	Chronic 3 days prior	Rat hippocampus, frontal cortex	NFkB activity	Peripheral LPS	(Munhoz in prep)
Low stress cort levels	Chronic 10 days	Rat hippocampus, cerebellum	5-lipoxygenase	None	(Uz et al. 1999)

The variety of experimental conditions in which GC enhanced inflammation has been observed makes definitive conclusions difficult. The top table is a non-comprehensive list of pro-inflammatory effects of GCs on peripheral immunity. The bottom table lists conditions where GCs have been found to enhance signs of central inflammation and is more extensive. The type of GC treatment varies between experimental groups; however broad categorizations have been assigned. Basal stress cort levels are between 1-10μg/dL, low stress cort levels are between 10–25μg/dL, and high stress cort levels are above 25μg/dL. Dexamethasone doses are roughly equivalent to high stress cort doses at 10⁻⁷M. Importantly, enhanced inflammation due to acute stress is not necessarily attributable to GCs. GC treatment time refers to the time of exposure to GCs relative to a subsequent inflammatory stimulus or measurement. See text for a more detailed description of many of these investigations.

^*study potentially affected by poor BBB permeability of dexamethasone (see text).

Ab = antibody; cort = corticosterone (in rodent studies) or cortisol (in primate studies); CUS = chronic unpredictable stress; IL = interleukin; LPS = lipopolysaccharride; MAPK = mitogen-activated protein kinase;, MIF = macrophage migration initiation factor; NFkB = nuclear factor kappa B; PBMC = peripheral blood mononuclear cells; PGD2= prostaglandin D2; PMA is the NFkB activator phorbol 12-myristate 13-acetate; THP-1 = human monocyte cell line; TMT = trimethyltin; TNF = tumor necrosis factor