Leptin and Cellular and Innate Immunity in Abstinent Alcoholics and Controls

Authors

  • Sarosh J. Motivala,

    Corresponding author
    1. Cousins Center for Psychoneuroimmunology (SJM, JD, AWB, MI), University of California–Los Angeles Neuropsychiatric Institute, Los Angeles, California; and Washington State University (TO, GGM), Pullman, Washington.
    Search for more papers by this author
  • Jeff Dang,

    1. Cousins Center for Psychoneuroimmunology (SJM, JD, AWB, MI), University of California–Los Angeles Neuropsychiatric Institute, Los Angeles, California; and Washington State University (TO, GGM), Pullman, Washington.
    Search for more papers by this author
  • Tanja Obradovic,

    1. Cousins Center for Psychoneuroimmunology (SJM, JD, AWB, MI), University of California–Los Angeles Neuropsychiatric Institute, Los Angeles, California; and Washington State University (TO, GGM), Pullman, Washington.
    Search for more papers by this author
  • Gary G. Meadows,

    1. Cousins Center for Psychoneuroimmunology (SJM, JD, AWB, MI), University of California–Los Angeles Neuropsychiatric Institute, Los Angeles, California; and Washington State University (TO, GGM), Pullman, Washington.
    Search for more papers by this author
  • Anthony W. Butch,

    1. Cousins Center for Psychoneuroimmunology (SJM, JD, AWB, MI), University of California–Los Angeles Neuropsychiatric Institute, Los Angeles, California; and Washington State University (TO, GGM), Pullman, Washington.
    Search for more papers by this author
  • Michael R. Irwin

    1. Cousins Center for Psychoneuroimmunology (SJM, JD, AWB, MI), University of California–Los Angeles Neuropsychiatric Institute, Los Angeles, California; and Washington State University (TO, GGM), Pullman, Washington.
    Search for more papers by this author

  • Supported in part by Grants AA10215, AA13239, MH55253, AG18367, AT00255, AR/AG41867, AA07293, T32 AA07557, and T32 MH17140 and by the Cousins Center for Psychoneuroimmunology.

Sarosh J. Motivala, PhD, Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute, Medical Plaza 300, Rm. 3160A, Box 957076, Los Angeles, CA 90095-7076; Fax: 310-794-9247; E-mail: smotivala@mednet.ucla.edu.

Abstract

Background: Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity.

Methods: Circulating levels of leptin, natural killer cell (NK) activity, interleukin-2 (IL-2)–stimulated NK activity, and concanavalin A–stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between abstinent DSM-IV alcohol-dependent men (n= 27) and age- and gender-matched controls (n= 34).

Results: As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p= 0.055). In the total sample, leptin predicted NK activity (β= 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n= 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone.

Conclusions: These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases.

Ancillary