Table 1.

Ethanol-induced changes in the brain cytokine gene expression and protein levels in the animal models and humans.

Animal models (rodents)
Cytokine	Ethanol Treatment	Brain region	Δ mRNA levels	Δ Protein levels
IL-1β	Acute	Whole brain	= [106, 110, 242] ↓ [242]	↑ [106] = [110] ↓ [242]
		Cortex	↑ [243] = [35, 243–245]	= [244, 246]
		Hypothalamus (PVN)	↑ [242] = [167, 242, 247] ↓ [247]	= [246]
		Hippocampus	↑ [242] = [167, 242, 247] ↓ [247]	= [246]
		Cerebellum	= [242]
		Amygdala	= [167, 247]
	Prolonged/Binge	Whole brain	= [248] [110]	= [110, 248]
		Cortex	↑ [35] = [225]	↑ [249–251]
		Hippocampus	↑ [225]	↑ [251]
		Cerebellum	↑ [39, 225]
		Striatum/NAc		↑ [249]
	Chronic	Cortex	↑ [244, 252] = [244] ↓ [223]	↑ [252–254] = [244, 252]
		Hypothalamus (PVN)	↓ [242]
		Hippocampus	= [242]	↑ [254, 255]
		Cerebellum	↑ [53]	↑ [53]
		Amygdala	↓ [242]
		Striatum/NAc		↑ [226]
IL-6	Acute	Cortex	= [245]	= [245]
		Hypothalamus (PVN)	↑ [242, 247] = [167, 242]
		Hippocampus	↑ [242, 247] = [167, 242, 247]
		Cerebellum	↑ [242] = [242] ↓ [242]
		Amygdala	↑ [247] = [167]
	Prolonged/Binge	Whole brain	↑ [248]	↑ [248]
		Cortex	= [221, 222]	↑ [178] = [178]
		Hypothalamus (PVN)		↑ [255]
		Hippocampus	= [221, 222]	= [178]
		Cerebellum	= [222]
	Chronic	Cortex		↑ [253]
		Hypothalamus (PVN)	= [242]	↑ [256]
		Hippocampus	= [242]	↑ [253]
		Amygdala	↑ [242]
IL-10	Acute	Whole brain	= [110]
		Hippocampus		↑ [176]
	Prolonged/Binge	Whole brain	= [110]	↓ [110]
		Cortex		= [38, 178]
		Hippocampus		↑ [178] = [38, 178]
		Cerebellum	= [39]
	Chronic	Cortex		↓ [253]
		Hippocampus		↓ [253]
IL-1Ra	Chronic	Cerebellum		↑ [53]
TNF-α	Acute	Whole brain	↑ [106, 110]	↑ [106] = [110]
		Cortex	↑ [243, 245] = [243–245]	↑ [244, 257] = [246]
		Hypothalamus (PVN)	↑ [242] = [167, 242] ↓ [242, 247]
		Hippocampus	↑ [242] = [167, 242] ↓ [242, 247]	= [246]
		Cerebellum	= [242] ↓ [242]
		Amygdala	= [167, 247] ↓ [247]
	Prolonged/Binge	Whole brain	↑ [110, 248] = [110]	↑ [110, 248] = [110]
		Cortex	↑ = [221, 222, 225]	↑ [35, 250, 251] = [38, 178]
		Hypothalamus (PVN)		↑ [255] = [258]
		Hippocampus	↑ [225] = [221, 222]	↑ [38, 250, 251] = [38, 178, 259]
		Cerebellum	↑ [39, 225] = [39, 222]
		Striatum/NAc		↑ [35]
	Chronic	Cortex	↑ [223, 244, 252] = [244]	↑ [252–254] = [244]
		Hypothalamus (PVN)	= [242]	↑ [256]
		Hippocampus	↓ [242]	↑ [253, 254]
		Cerebellum	↑ [53]	↑ [53]↓
		Amygdala	= [242]
		Striatum/NAc		↑ [226] = [226]
MCP-1/CCL2	Acute	Whole brain	↑ [110]	↑ [260] = [110, 260]
		Cortex	↑ [245] =[35] [222, 244, 245]	↑ [249] = [244]
		Hippocampus	↑ [222]
		Cerebellum	↑[222]
	Prolonged/Binge	Whole brain	↑ [110, 248]	↑ [110, 248] = [110]
		Cortex	↑ [35, 221, 225] = [221]	↑ [221]
		Hippocampus	↑ [221, 225] = [221] ↓	↑ [221]
		Cerebellum	↑ [225]
		Striatum/NAc		↑ [249]
	Chronic	Cortex	↑ [223, 244] = [244] ↓	↑ = [244] ↓
		Cerebellum	↑ [53]	↑ [53]
		Striatum/NAc		↑ [226]
Humans
Cytokine	Ethanol Anamnesis	Brain region	Δ mRNA levels	Δ Protein levels
IL-1β	Alcoholics –acutely exposed to EtOH	CF		= [219]
	Alcoholics (postmortem)	Hippocampus		↑ [74]
IL-6	Alcoholics + hepatic encephalopathy	Superior frontal gyrus		=[261]
		Precentral gyrus		= [261]
IL-10	Alcoholics + hepatic encephalopathy	Superior frontal gyrus		=[261]
		Precentral gyrus		= [261]
TNF-α	Alcoholics –acutely exposed to EtOH	CF		= [219] ↓ [219]
MCP-1/CCL2	Alcoholics (postmortem)	VTA		↑ [218]
		Substantia nigra		↑ [218]
		Hippocampus		↑ [218]
		Amygdala		↑ [218]
	Alcoholics –acutely exposed to EtOH	CF		↑ [219]

Table 1. We define “Acute treatment” as a single administration or continuous application for less than 24 hrs. The “Prolonged/Binge treatment” includes several binge models and repeated ethanol exposure for less than 2 weeks, and “Chronic treatment” corresponds to ethanol treatments exceeding 2 weeks. The primary reasons for the discrepancies in the direction of the ethanol effects on a particular cytokine among and within the studies include age (e.g. adolescent vs adult), sex, ethanol treatment/administration (e.g. intraperitoneal vs intragastric application, or continuous vs intermittent treatment), and posttreatment time of the tissue collection (e.g. 1 day vs 28 days). The references in red correspond to the mouse studies and references in black to the studies in rats. The term “Cortex” encompasses findings from the studies on the neocortex, frontal cortex, mPFC, entorhinal and temporal cortex. We mark the direction of the ethanol effects on the cytokines (Δ mRNA/protein levels) as ↑ - increase, = - no change, and ↓ - decrease in the mRNA or protein levels. Abbreviations: CF – cerebrospinal fluid, VTA – ventral tegmental area, PVN – Paraventricular nucleus of the hypothalamus, NAc – Nucleus accumbens.