Table 3.

In vivo effects of melatonin on inflammatory conditions.

	Inflammatory condition	Melatonin effects	Molecular mechanism	References
Rat	Exercise-induced cardiac inflammatory injury	Reduces TNF-α, IL-1β and IL-6 production		[111]
	Experimental colitis	Counteracts the high production of TNF-α, IL-1 and NO	Downregulation of NF-κB	[112]
	Diabetes-associated low-grade inflammation	Lowers TNF-α, IL-6 and CRP		[113]
	Experimental model of traumatic brain injury	Reduces upregulation of IL-6, iNOS, SOCS-3 and oxidative stress	Overcomes STAT-1 inactivation	[114]
	Heatstroke-induced multiple organ dysfunction syndrome	Attenuates high production of TNF-α, IL-1β and IL-6 and promotes IL-10 production		[94]
	Ischemia reperfusion-induced liver damage	Attenuates enhanced levels of TNF-α, IL-6 and NO	Suppresses the increase in MyD88, ERK, phosphorylated JNK and c-Jun and nuclear translocation of NF-κB	[115]
	Neuroinflammation in experimental diabetic neuropathy	Attenuates elevated levels of TNF-α, IL-6, iNOS, COX-2 and oxidative stress	Decreases NF-κB cascade activation	[116]
	FK506-induced nephropathy	Lowers TNF-α, IL-6 and NO levels		[117]
	Acetic acid-induced colitis	Reverses increased levels of TNF-α, IL-1β, IL-6, MPO and oxidative stress		[118]
	Cerulein-induced pancreatitis	Reduces expression of TNF-α, IL-1β, IL-6, IL-8 and iNOS	Inhibition of elevated nuclear binding of NF-κB	[119]
	Hemorrhagic shock	Suppresses the release of TNF-α and IL-6		[120]
	DMN-induced liver injury	Decreases expression of TNF-α, IL-1β, IL-6 and iNOS	Inhibition of increased nuclear binding of NF-κB	[121]
	Aging	Attenuates increased levels of TNF-α, IL-1β, IL-6, iNOS and LPO		[122]
	Cecal dissection-induced bacterial peritonitis	Lowers levels of TNF-α, IL-6 and MDA		[123]
	Pancreatic fluid-induced lung inflammation and airway hyperreactivity	Reduces TNF-α and iNOS concentrations		[95]
	TNBS-induced colitis	Decreases high levels of TNF-α, IL-1 and NO	NF-κB inhibition and blockade of IκBα degradation	[112,124]
	Neuro-inflammation induced by intra-cerebroventricular administration of LPS	Decreases TNF-α, IL-1β and oxidative stress		[125]
	Experimental periodontitis	Reduces TNF-α, IL-1β and MDA		[126]
	DNBS-induced colon injury	Reduces expression of TNF-α and MMP-9 and MMP-2 activities	Reduction in NF-κB activation and phosphorylation of c-Jun	[127,128]
	Taurocholate-induced acute pancreatitis	Reduces TNF-α and amylase levels		[129]
	Escherichia coli-induced pyelonephritis	Reverses increased levels of TNF-α and MDA		[130]
	Spinal cord injury	Decreases expression of TNF-α and MMP-9 and MMP-2		[127]
	Lung ischemia-reperfusion injury	Diminishes levels of TNF-α	Inhibition of NF-κB protein levels	[131]
	Hypoxia-induced retinal ganglion cell death	Reverses the upregulation of TNF-α, IL-1β and LPO		[132]
	Mechlorethamine-induced nephrotoxicity	Ameliorates the increased production of TNF-α and IL-1β		[133]
Mouse	Immunological liver injury	Attenuates the increases in TNF-α and IL-1β		[134]
	Radiation-induced lung injury	Reduces TNF-α, TGF-1 and oxidative stress		[135]
	Maternal LPS-induced inflammation	Attenuates elevation of TNF-α in maternal serum and fetal brain		[136]
	Indomethacin-induced chronic gastric ulcer	Blocks expression of TNF-α, IL-1β and IL-8	Inhibition of ERK and JNK phosphorylation and NF-κB, c-Fos and c-Jun expression	[137]
	Alzheimer’s transgenic mice	Decreases TNF-α levels in hippocampus		[138]
Human	Infant endotracheal intubation	Lowers IL-6, IL-8, IL-10 and IL-12		[139]
	Strenuous exercise	Prevents overexpression of TNF-α, IL-6, IL-1ra and oxidative stress		[140]
	Duchenne muscular dystrophy	Reduces levels of TNF-α, IL-1β, IL-6, IL-2, IFN-γ and oxidative stress		[141]
	Respiratory distress syndrome	Limits serum rise in TNF-α, IL-6 and IL-8		[142]

CRP: C-reactive protein; MPO: myeloperoxidase; NO: nitric oxide; DMN: dimethylnitrosamine; TNBS: 2,4,6-trinitrobenzenesulfonic acid; DNBS: dinitrobenzene sulfonic acid; empty spaces indicate unknown molecular mechanisms.