OBJECTIVESInvoluntary weight loss affects 20% of community dwelling older adults. The underlying mechanism for this disorder is unknown. Objective is to determine if failure of older persons to regain weight is associated with elevated pro-inflammatory cytokine and leptin levels.DESIGNProspective diet intervention study.SETTINGUniversity of Washington Medical Center from 2001-2005.PARTICIPANTSTwenty-one younger (18-35 years old) and nineteen older (>or= 70 years old) men and women.INTERVENTIONEach subject was placed for two weeks on a weight-maintaining diet, followed in sequence by 2 weeks of 30% caloric restriction, then 4 weeks of ad libitum food intake.MEASUREMENTSPlasma leptin levels, fasting serum pro-inflammatory cytokine levels, and peripheral blood mononuclear cell cytokine levels were measured.RESULTSLeptin levels in the two cohorts decreased after caloric restriction and increased after ad-libitum food consumption resumed. Plasma TNF alpha levels were higher in older subjects compared to younger adults. However, there was no association between changes in TNF alpha levels and changes in AUC leptin.CONCLUSIONLeptin levels in healthy older individuals responded appropriately in a compensatory manner to changes in body weight. These data do not support a cytokine dependent elevation in leptin levels as being responsible for the failure of older adults to regain weight.