Alcoholism: A systemic proinflammatory condition

Table 1 Central nervous system alterations in alcoholic patients

Anatomo-clinical forms of chronic central nervous system damage	Brain cortical and subcortical atrophy
	Cerebellar degeneration
	Decreased blood flow
	Pellagra
	Wernicke-Korsakoff encephalopathy
	Marchiafava-Bignami disease
	Central pontine myelinolysis
	Increased prevalence of stroke
	Cerebral trauma
Clinical features of brain atrophy	May vary from frank dementia to subtle alterations
	Reversible with prolonged ethanol withdrawal
Underlying anatomic lesions of brain atrophy	Neuronal death
	Apoptosis
	Decreased neuronogenesis
	White matter alterations
Main mechanisms of brain atrophy	Effects of ethanol and lipopolysaccharide
	Cytokine (especially TNF-α) mediated neuroinflammation.
	Oxidative damage (mainly ethanol-mediated), iron excess
	Vitamins (antioxidants?) deficiency
	Protein deficiency and malnutrition?
	Excitotoxicity?
	Co-existing liver disease?

TNF: Tumor necrosis factor.

Table 2 Main factors involved in ethanol-associated osteopenia

Factors	Main mechanism(s) involved
Direct effect of ethanol	Direct effect on osteoblast function (oxidative damage). Possible effect on bone resorption (cytokines)
Liver disease	Decreased absorption of proteins, calcium, vitamin D, nutrients in general
	Altered hormonal profile (altered IGF-1, vitamin D, gonadal hormones)
Chronic pancreatitis	Altered absorption. Malnutrition
Malnutrition	Decreased osteoid synthesis. Decreased IGF-1 levels. Altered nutrient intake. Altered absorption. Increased cytokine levels?
Alcoholic hypogonadism	Altered trophic effect on bone and muscle
Alcoholic myopathy/neuropathy	Altered trophic effect on bone (probably via Wnt β catenin pathway)
Iron excess (increased absorption)	Interference with osteoblast function
Zinc deficiency (malnutrition; alcohol?)	Possibly, defective protein synthesis
Cytokines (IL-6; TNF-α)	Possibly, increased bone resorption
Lifestyle	Trauma. Bone fractures. Impaired nutrient intake

IGF: Insulin-like growth factor; TNF: Tumor necrosis factor; IL: Interleukin.