Hypothesis: Volunteers with vitamin D insufficiency (serum 25(OH)D 25-50 nmol/L) given intermediate or high dose vitamin D supplements (2,000 or 5,000 IU per day) will have increased production of anti-bacterial peptides and interleukin-1, decreased production of other pro-inflammatory cytokines, increased production of regulatory cytokines and an enhanced T- and B-cell response to a tetanus vaccine compared to vitamin D insufficient subjects given low dose vitamin D supplements (400 IU per day).

Specific Aim 1: Determine if high dose vitamin D supplements decrease the production of proinflammatory and increase the production of regulatory cytokines and chemokines by innate immune cells stimulated ex vivo. Specific Aim 2: Determine if high dose vitamin D supplements decrease serum markers of inflammation and increase serum and cellular levels of defensive molecules (e.g., cathelicidin). Specific Aim 3: Determine if high dose vitamin D supplements decrease blood levels of proinflammatory T-helper type 1 (Th1) and Th17 cells and increase levels of anti-inflammatory T-regulatory (Treg) and Th2 cells. Specific Aim 4: Determine if high dose vitamin D supplements increase antigen specific T cell and B cell responses after tetanus vaccination.