Table 1. Effects of histone deacetylase inhibitors in inflammatory and autoimmune diseases.

Disease model	Species	Inhibitor	Effects
Endotoxin	Human, mouse	SAHA	Reduced cytokine production (TNF- α, IL-1β, IL-6, IFN-γ) and lethality in vivo in mice77-79; decreased cytokine production in vitro using human PBMC78
ConA hepatitis	Mouse	SAHA	Decreased liver injury78
Airway hypersensitivity	Mouse	TsA	Decreased allergen-induced airway inflammation in a model of asthma, with decreased airway hyperresponsiveness, mucus production, leukocyte infiltration and cytokine production93
Experimental autoimmune encephalomyelitis	Mouse	TsA	Decreased demyelination, leukocyte infiltration and TH1 cytokine and chemokine production in relapsing phase of experimental autoimmune encephalomyelitis94
Stroke	Mouse	SAHA, TsA	Decreased infarct size post-middle cerebral artery occlusion103
Neurodegenerative diseases	Mouse	Butyrate106,107, SAHA105	Decreased disease progression in models of Huntington’s chorea105, spinal and muscular dystrophy106, amyotrophic lateral sclerosis107
Colitis	Mouse	SAHA, TsA	Decreased weight loss, histological injury, leukocyte infiltration and cytokine production in dextran sodium sulphate- and,4,6- trinitrobenzene sulphonic acid-induced colitis and adoptive transfer models7,26,96
Glomerulonephritis	Mouse	SAHA, TsA	Decreased proteinuria in MRL/lpr model of systemic lupus erythematosus, and decreased leukocyte infiltration and production of inflammatory mediators95
Arthritis	Mouse, rat	FK22897, SAHA and MS27598, VPA19,	Decreased joint swelling and bone and cartilage destruction in antibody-97 and collagen-induced28,98 models of arthritis, in conjunction with decreased overall leukocyte infiltration and TH1 cytokine and chemokine production, but increased Foxp3+ Treg accumulation19
Graft-versus-host disease	Mouse	SAHA	Decreased graft-versus-host disease99 and decreased CD3 monoclonal antibody-induced cytokine storm during bone marrow conditioning100
Transplant rejection	Mouse	SAHA, TsA,	Permanent engraftment of cardiac and islet allografts and Foxp3+ Treg-dependent tolerance induction7
Haemorrhage and resuscitation	Human, mouse, rat, pig	Butyrate, SAHA, TsA, VPA	Optimal protective effects with SAHA compared with TsA or VPA in a rat model109; SAHA-induced suppression of TNF-α production in rats but variable effects in humans110; VPA-associated increased expression of multiple protective genes in additional studies using pig111 and rat112 models, including BCL2 and HSP70 (REF. 111)

CD3, cluster of differentiation 3; HSP70, heat shock protein 70; IFN, interferon; IL, interleukin; PBMC, peripheral blood mononuclear cell; SAHA, suberoylanilide hydroxamic acid; TNF, tumour necrosis factor; T_reg, regulatory T cell; T_H1, type 1 helper T cell; TsA, trichostatin A (TsA); VPA, valproic acid.